KR102325944B1 - Anti-ceacam1 antibody and use thereof - Google Patents

Abstract

The present invention relates to an anti-CEACAM1 antibody with improved specific binding ability to CEACAM1 and uses thereof. The anti-CEACAM1 antibody according to the present invention has excellent specific binding ability to CEACAM1, cytotoxic T cells and natural killer cells. It can be usefully used as an anti-cancer agent and a composition for cancer treatment by activating the anti-cancer immune function.

Description

ANTI-CEACAM1 ANTIBODY AND USE THEREOF

The present invention relates to anti-CEACAM1 antibodies specifically binding to CEACAM1 and uses thereof.

Carcinoembryonic antigen-related cell adhesion molecule 1 (hereinafter, CEACAM1) belongs to the carcinoembryonic antigen group and is one of the transmembrane glycoproteins in the living body. CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7 and CEACAM8 are expressed in humans. At this time, CEACAM1 is mainly expressed in activated T cells and natural killer cells, and shows high expression in cancer cells. In addition, it shows low expression in epithelial cells, endothelial cells, and hematopoietic stem cells. In addition, CEACAM1 plays a role in the regulation of innate and adaptive immune responses. Specifically, CEACAM1 was found to be an inhibitory receptor for activated T cells contained within the human intestinal epithelium (Morales et al ., J. Immunol , 1999, 163, 1363-1370).

In addition, CEACAM1 activates immune checkpoint pathways as immune checkpoint substances such as PD-1 and CTLA-4. The immune checkpoint pathway protects tissues from damage by the immune system under physiological conditions. In addition, the pathway may include a variety of co-stimulatory and inhibitory molecules to maintain self-tolerance. When CEACAM1 is activated, the immune response can be avoided by suppressing the cytotoxicity of lymphocytes through the interaction between T cells and natural killer cells. Therefore, inhibiting the immune checkpoint pathway in cancer cells has emerged as a promising anticancer therapeutic strategy.

Studies of several human tumor types have reported that tumors can evade immunity by exploiting the CEACAM1 signaling pathway. In addition, in preclinical animal models of tumors, it has been shown that if the CEACAM1 interaction is blocked using a monoclonal antibody (mAb), the immune response to the tumor can be enhanced.

On the other hand, in the case of existing anticancer drugs, the side effects are very large compared to the anticancer effect. On the other hand, therapeutics that block immune checkpoints, which have recently been in the spotlight, attack cancer cells by activating inactivated immune cells instead of directly killing cancer cells. In the case of Merck's Keytruda treatment, the side effects are minimal compared to existing anticancer drugs, but the anticancer effect is excellent. Specifically, the treatment for Keytruda uses a PD-1 inhibitory antibody, Pembrolizumab. As a result of conducting a phase 2 clinical trial on a melanoma patient group using this, the anticancer response rate was 4% for chemotherapy, but 25% (2 mg/kg) to 87% (10 mg/kg) for Keytruda treatment. The reaction rate was shown.

On the other hand, when a CEACAM1 inhibitory antibody acts on cytotoxic T cells, natural killer cells, and CEACAM1 expressed on the surface of cancer cells, which play a major role in anticancer immune function, the CEACAM1 inhibitory antibody under development recognizes CEACAM3 and CEACAM5 in addition to CEACAM1. This is due to the characteristic binding to the N-domain with high homology between CEACAM1, CEACAM3 and CEACAM5.

Morales et al., J. Immunol, 1999, 163, 1363-1370

Therefore, in order to develop an anti-CEACAM1 antibody that specifically binds to CEACAM1, the present inventors found that the anti-CEACAM1 antibody binds to the N-domain and B-domain of CEACAM1 and has no cross-reactivity with CEACAM3, CEACAM5, CEACAM6 and CEACAM8. By confirming, the present invention was completed.

In order to achieve the above object, the present invention provides a light chain CDR1 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 8; a light chain CDR2 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 9 to 16; a light chain CDR3 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 17 to 29; a heavy chain CDR1 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 30 to 38; a heavy chain CDR2 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 39 to 46; And it provides an anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR3 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 47 to 55.

In addition, the present invention provides an anticancer agent comprising the anti-CEACAM1 antibody or fragment thereof as an active ingredient.

Furthermore, the present invention provides an anticancer adjuvant comprising the anti-CEACAM1 antibody or fragment thereof as an active ingredient.

In addition, the present invention provides a cancer treatment composition comprising the anticancer adjuvant and cell therapy agent.

Furthermore, the present invention provides a method of treating cancer, comprising administering to a subject the lymphocytes contacted with the anti-CEACAM1 antibody or fragment thereof.

In addition, the present invention provides a method for inhibiting the proliferation of CEACAM1-expressing tumor cells, comprising the step of contacting the CEACAM1-expressing tumor cells with the anti-CEACAM1 antibody or antibody fragment.

The anti-CEACAM1 antibody according to the present invention not only specifically binds to CEACAM1, but also activates the anticancer immune function of cytotoxic T cells and natural killer cells, so that it can be usefully used as an anticancer agent and a composition for treating cancer.

1a is a schematic diagram of the structure of recombinant CEACAM1 prepared according to one embodiment.
1B is a diagram showing the binding capacity of an anti-CEACAM1 antibody according to the constitutive domains of recombinant CEACAM1.
2 is a view confirming the binding of an anti-CEACAM1 antibody according to the CEACAM1 protein concentration.
3 is a diagram showing the binding affinity of CEACAM1 and C25 expressed on the surface of the Jurkat E6.1 T cell line according to the concentration of C25.
4 is a diagram showing the affinity between the anti-CEACAM1 antibody and CEACAM1. Affinity was obtained as the kinetic rate constants K _on and K _off and the equilibrium dissociation constant K _D .
5 is a photograph showing the isoelectric point of C25. Lane 1 is IEF-Markers 3-10, Lane 2 is huIgG4, Lane 3 is C25.
6 is a view confirming T-cell activation according to anti-CEACAM1 antibody treatment through TCR-induced NFAT activation.
7 is a view showing the increase in NFAT receptor activity of T cells according to the anti-CEACAM1 antibody treatment compared to the control group.
8A is a photograph stained with C25 to confirm the expression level of CEACAM1 in normal tissues of humans and monkeys.
Figure 8b is a photograph of normal tissues of humans and monkeys stained with huIgG4.
9 is a view confirming the cross-reactivity between the anti-CEACAM1 antibody and the CEACAM family protein.
10 is a view confirming the cross-reactivity between the anti-CEACAM1 antibody and the CEACAM family protein.
11 is a view confirming that C25 has no cross-reactivity with CEACAM3, CEACAM5, CEACAM6 and CEACAM8.
12 is a view confirming that C25 binds to CEACAM1 in monkeys as well as humans.
Figure 13a is a diagram showing the enhancement of the anticancer effect of TALL-104 T cells by C25.
Figure 13b is a diagram showing the enhancement of the anticancer effect of NK92MI cells by C25.

Hereinafter, the present invention will be described in detail.

The present invention provides a light chain CDR1 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 8; a light chain CDR2 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 9 to 16; a light chain CDR3 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 17 to 29; a heavy chain CDR1 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 30 to 38; a heavy chain CDR2 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 39 to 46; And it provides an anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR3 comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 47 to 55.

In addition, as used herein, the term "antibody" refers to an immune protein that binds to an antigen and interferes with the action of the antigen or removes the antigen. There are five types of antibodies: IgM, IgD, IgG, IgA, and IgE, each containing heavy chains made from heavy chain constant region genes μ, δ, γ, α, and ε. In antibody technology, IgG is mainly used, and there are four isotypes of IgG1, IgG2, IgG3, and IgG4, and the structure and functional properties of each may be different.

In addition, the IgG forms a very stable Y-shaped structure (molecular weight, about 150 kDa) made of two heavy chain (heavy chain, about 50 kDa) proteins and two light chain (about 25 kDa) proteins. The light and heavy chains of an antibody are divided into a variable region having a different amino acid sequence for each antibody and a constant region having the same amino acid sequence. The heavy chain constant region includes CH1, H (hinge), CH2, CH3 domains. Each domain consists of two β-sheets and is connected by intramolecular disulfide bonds. The two variable regions of the heavy and light chains combine to form an antigen binding site. The region exists in each of the two arms of the Y-shape, and the part capable of binding to the antigen is called an antibody binding fragment (Fab), and the part that cannot bind to the antigen is called a crystalizable fragment (Fc). Fab and Fc are connected by a flexible hinge region.

In addition, the term "CDR" used in the present invention refers to a region that binds to an antigen as a hypervariable region, which is a region having a different amino acid sequence for each antibody in the heavy and light chain variable regions of an antibody. Looking at the three-dimensional structure of the antibody, the CDRs are in the shape of a loop on the surface of the antibody, and there is a framework region (FR) that structurally supports them under the ring. Each of the heavy and light chains has three ring structures, and these six ring region structures combine with each other to make direct contact with the antigen.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, and an amino acid sequence shown in SEQ ID NO: 17 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 56 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 106 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, and an amino acid sequence shown in SEQ ID NO: 18 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 58 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 107 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, and an amino acid sequence shown in SEQ ID NO: 19 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 60 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 108 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, and an amino acid sequence shown in SEQ ID NO: 20 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 62 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 109 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, and an amino acid sequence shown in SEQ ID NO: 17 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 110 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, and an amino acid sequence shown in SEQ ID NO: 21 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 66 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 111 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or its antibody light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 11, and the amino acid sequence shown in SEQ ID NO: 22 light chain CDR3, heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, and heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47.

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 68 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 112 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, and an amino acid sequence shown in SEQ ID NO: 17 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 48 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 88. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 110 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 122.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, and an amino acid sequence shown in SEQ ID NO: 17 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 31, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 90. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 110 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 123.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 2, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 12, and an amino acid sequence shown in SEQ ID NO: 24 a light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 32, a heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 40, and a heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 49 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 72 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 92. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 114 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 124.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 3, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 13, and an amino acid sequence shown in SEQ ID NO: 25 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 33, heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 33, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 41, and heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 50 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 74 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 94. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 115 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 125.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 4, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 14, and an amino acid sequence shown in SEQ ID NO: 23 a light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 34, a heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 42, and a heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 51 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 76 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 96. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 116 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 126.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 15, and an amino acid sequence shown in SEQ ID NO: 26 a light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 35, a heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 43, and a heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 52 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 78 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 98. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 117 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 127.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 6, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 16, and an amino acid sequence shown in SEQ ID NO: 27 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 36, heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 36, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 44, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 53 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 80 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 100. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 118 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 128.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 7, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 14, and an amino acid sequence shown in SEQ ID NO: 28 It may include a light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 37, a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 37, a heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 45, and a heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 54 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 82 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 102. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 119 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 129.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 8, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 15, and an amino acid sequence shown in SEQ ID NO: 29 a light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 38, a heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 46, and a heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 55 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 84 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 104. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 120 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 130.

Specifically, the anti-CEACAM1 antibody or fragment thereof comprises a light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, and an amino acid sequence shown in SEQ ID NO: 23 light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 30, heavy chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 39, heavy chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 47 .

In addition, the antibody or fragment thereof may include a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 70 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86. However, if the CDR1, CDR2, and CDR3 of the heavy chain variable domain are identical, the framework portion can be modified. In particular, in order to prepare a humanized antibody, the amino acid sequence of some framework parts may be modified.

In addition, the antibody or fragment thereof may include a light chain including the amino acid sequence represented by SEQ ID NO: 113 and a heavy chain including the amino acid sequence represented by SEQ ID NO: 121.

In addition, the antibody fragment may be any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} Antibody fragment refers to antigen-binding domains excluding the determinable region (Fc region) that has an effector function to transmit antigen-binding stimulation to cells or complement, single domain antibody or minibody ), etc., may include third-generation antibody fragments.

In addition, the antibody fragment has a good penetration rate into tissues or tumors because it has a smaller size compared to the complete IgG, and has the advantage of low production cost because it can be produced in bacteria, and because there is no Fc, stimulation of antigen binding to cells It is used when you do not want the function to deliver to or complement. Antibody fragments have a short half-life in the human body and are suitable for biodiagnosis, but if some basic, acidic, or neutral amino acids of the amino acids constituting the antibody are replaced with each other, the unique isoelectric point (pI) of the antibody may change. have. Since the change in the isoelectric point of the antibody can induce changes such as reducing the toxic side effects or increasing the water solubility of the antibody, in the case of a therapeutic antibody, a complete IgG can be used in consideration of affinity or structural form.

In addition, the light chain variable domain of the anti-CEACAM1 antibody or fragment thereof of the present invention is represented by SEQ ID NO: 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82 or 84 It may have 97%, 98% or 99% homology to a light chain variable domain sequence comprising an amino acid sequence of

In addition, the heavy chain variable domain of the anti-CEACAM1 antibody or fragment thereof of the present invention comprises a heavy chain variable domain sequence comprising the amino acid sequence represented by SEQ ID NO: 86, 88, 90, 92, 94, 96, 98, 102 or 104, or and at least 97%, 98% or 99% homology to the heavy chain variable domain sequence.

In addition, the anti-CEACAM1 antibody or fragment thereof of the present invention has an amino acid sequence represented by SEQ ID NO: 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82 or 84 have at least 97%, 98% or 99% homology to a light chain variable domain sequence comprising a light chain variable domain sequence comprising can

In addition, the anti-CEACAM1 antibody refers to an antibody that binds to CEACAM1. The term "C25" used in the present invention is an embodiment of the anti-CEACAM1 antibody.

In addition, the anti-CEACAM1 antibody or fragment thereof recognizes the N-domain and B-domain of CEACAM1 as antigenic determinants (epitope). In addition, the antibody is not cross-reactive with CEACAM3, CEACAM5, CEACAM6 and CAECAM8.

In addition, the anti-CEACAM1 antibody of the present invention can be easily prepared by a known monoclonal antibody production technique. The method for preparing a monoclonal antibody may be performed by preparing a hybridoma using B lymphocytes obtained from an immunized animal, or may be performed by using a phage display technology, but is not limited thereto.

In addition, the present invention provides an anti-cancer agent comprising an anti-CEACAM1 antibody or fragment thereof as an active ingredient.

The anti-cancer agent comprising the anti-CEACAM1 antibody or fragment thereof of the present invention as an active ingredient may be used to treat CEACAM1 overexpressed cancer or tumor. Specifically, when the T-cell receptor (TCR) of cytotoxic T cells, which plays a role in eliminating cancer cells, recognizes the antigenic determinant of cancer or tumor cells, it is located at the end of the cluster of differentiation 4 (CD4), one of the components of TCR. The bound LCK (lymphocyte-specific protein tyrosine kinase) protein phosphorylates another component of the TCR, cluster of differentiation 3ζ (CD3ζ). When the ZAP70 (Zeta-chain-associated protein kinase 70) protein is bound to the phosphorylated CD3ζ portion, the end of the ZAP70 protein is phosphorylated again by the LCK protein, and the RAS-MAPK signaling mechanism (Ras-MAP kinase signal transduction) is activated and T cells are activated

However, in the case of cancer cells or tumor cells overexpressing CEACAM1, the immunoreceptor tyrosine-based inhibition motif (ITIM) portion of CEACAM1 phosphorylated by the LCK protein bound to the CD4 terminus of the TCR due to the CEACAM1-CEACAM1 interaction was added to the Src homology (SHP1) portion. region 2 domain-containing phosphatase-1) protein is bound. In addition, the CD3ζ terminus is dephosphorylated by the SHP1 protein, and the RAS-MAPK signaling mechanism is not activated, so that the T cells are not activated.

Therefore, the anti-CEACAM1 antibody or fragment thereof binds to CEACAM1 expressed in cytotoxic T cells, natural killer cells, and cancer cells, and thus can be used as an anticancer agent by blocking the CEACAM1-CEACAM1 interaction in advance.

In addition, the term "anticancer" as used in the present invention includes 'prevention' and 'treatment', where 'prevention' refers to any action that inhibits the growth of cancer or delays the progression of cancer by administering the anticancer agent. means, and 'treatment' refers to any action in which the symptoms of cancer are improved or beneficially changed by administration of the antibody of the present invention.

In addition, the term "cancer" used in the present invention may be characterized as selected from the group consisting of pancreatic cancer, melanoma, lung cancer and myeloma, but is not limited thereto, and has CEACAM1 as a receptor and immune checkpoint pathway abnormally The cancer or tumor to be operated is not particularly limited, and may include solid cancer and hematological cancer.

In addition, the present invention provides an anti-cancer adjuvant comprising an anti-CEACAM1 antibody or fragment thereof as an active ingredient.

In addition, there is provided a cancer treatment composition comprising the anticancer adjuvant and cell therapy agent. The cell therapy agent may include cytotoxic T cells or natural killer cells.

In addition, the term "cell therapy agent" used in the present invention refers to the biological characteristics of cells by proliferating and selecting living autologous, allogenic, and xenogenic cells in vitro to restore the functions of cells and tissues. It refers to medicines used for preventive and therapeutic purposes through a series of actions that change the Specifically, it may be a cytotoxic T cell or a natural killer cell.

Also provided is a method of treating cancer using the anti-CEACAM1 antibody or fragment thereof of the present invention. Specifically, the method may include administering to the subject the lymphocytes contacted with the anti-CEACAM1 antibody or fragment thereof of the present invention. The lymphocyte is a type of white blood cell, which accounts for about 25% of the total white blood cell, and may be a natural killer cell, a T cell, or a B cell. In addition, the lymphocytes may be obtained from an individual. Preferably, it may be characterized in that it contains at least one of cytotoxic T cells or natural killer cells. The cancer is as described above.

In addition, the term "individual" used in the present invention refers to a person suffering from a disease or a state in which the disease can be alleviated, suppressed, or treated by administering the anticancer adjuvant of the present invention.

In addition, as used herein, the term "contacting" means mixing an anti-CEACAM1 antibody or fragment thereof with cells expressing CEACAM1.

In addition, the term "administration" as used in the present invention means introducing an effective amount of a substance into a subject by an appropriate method, and the administration route of the composition comprising the anti-CEACAM1 antibody or fragment thereof of the present invention reaches a target tissue It can be administered through a common route that can be administered. Specifically, depending on the intended use, parenteral administration (eg, intravenous, subcutaneous, intraperitoneal or topical administration) may be used, and preferably intravenous administration. In some cases, in administration to solid cancer, topical administration may be desirable to facilitate rapid and easy access of the antibody. The dosage varies according to the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease. A single dose may be administered in an amount of about 0.001 to 10 mg/kg on a daily or weekly basis. The effective amount may be adjusted at the discretion of the physician treating the patient.

In addition, the composition for treating cancer according to the present invention may be administered in a pharmaceutically effective amount to treat cancer cells or their metastases, or to inhibit the growth of cancer. It may vary depending on various factors such as cancer type, patient's age, weight, characteristics and severity of symptoms, type of current treatment, number of treatments, dosage form, and route, and may be easily determined by experts in the field.

The composition of the present invention may be administered together or sequentially with the aforementioned pharmacological or physiological components, or may be administered in combination with an additional conventional therapeutic agent, or may be administered sequentially or simultaneously with the conventional therapeutic agent. Such administration may be single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, and can be easily determined by those skilled in the art.

In addition, the present invention provides a method for inhibiting proliferation of CEACAM1-expressing tumor cells using an anti-CEACAM1 antibody or fragment thereof. Specifically, the method may include contacting a tumor cell expressing CEACAM1 with an anti-CEACAM1 antibody or a fragment thereof.

Hereinafter, the present invention will be described in detail by way of Examples. However, the following examples are only for illustrating the present invention, and the present invention is not limited to the following examples.

Example 1. Anti- CEACAM1 Antibody (C25)

Example 1.1 Preparation of anti-CEACAM1 antibody

SEQ ID NO: 57, 59, 61, 63, including the sequence recognized by each restriction enzyme through PCR of the antibody fragment gene inserted in the form of scFv (single-chain variable fragment) in the pComb3X vector (Addgene; Cat. #63891) A light chain variable region gene represented by 65, 67, 69, 71, 73, 75, 77, 79, 81, 83 or 85 and SEQ ID NO: 87, 89, 91, 93, 95, 97, 99, 101, 103 or 105 A heavy chain variable region gene represented by was obtained. The heavy chain gene was treated with NotI and ApaI restriction enzymes, and the light chain gene was treated with NotI and BamHI restriction enzymes.

The heavy chain gene and the light chain gene were inserted into pcIW vector (Promega; Cat. #E1731) cut with the same restriction enzyme as the heavy or light chain gene. Thereafter, a vector containing both a heavy chain transcription unit and a light chain transcription unit was selected using a restriction enzyme. The selected vector was extracted using the QIAGEN Plasmid Plus Midi Kit (QIAGEN; Cat. # 12943), and the nucleotide sequence of the antibody was finally confirmed through sequencing using some of the extracted DNA. The amino acid sequence of the antibody was analyzed through the nucleotide sequence. The amino acid sequences and nucleotide sequences of the analyzed antibodies are shown in Tables 1 and 2.

30 ㎍ of the extracted antibody DNA was treated and transfected with 30 ㎖ of ExpiHEK293F cells (ThermoFisher scientific; Cat. # A14527) at a concentration of ^{2.5x10 6 cells/ml.} The day after transfection, an enhancer (enhancer, ThermoFisher; Cat. # A14524) was added to the transfected ExpiHEK293F cells and incubated _{for 7 days at 37° C., CO 2} 8%, 125 rpm in a stirred incubator to produce anti-CEACAM1 antibody. .

After incubation, the supernatant separated by centrifugation from the culture medium was reacted with 100 μl of protein A beads (Repligen; Cat.# CA-PRI-0100) for 2 hours. Then, the beads were washed with 10 ml of binding buffer (ThermoFisher scientific; Cat. # 21019). After that, 200 ml of elution buffer (ThermoFisher scientific; Cat. # 21004) was added to the beads to separate the antibody conjugated to the beads. The isolated antibody was neutralized by adding 10 μl 1.5 M Tris-HCl pH 8.8 solution (Bio-rad; Cat. # 210005897).

Experimental example 1. Anti- CEACAM1 Check the binding affinity of the antibody

Experimental Example 1.1. Confirmation of binding affinity of anti-CEACAM1 antibody according to domain of CEACAM1

30 ㎍ of the DNA of the CEACAM1 mutant proteins conjugated with the human immunoglobulin Ckappa domain was treated with 30 ㎖ of ExpiHEK293F (ThermoFisher scientific; Cat. # A14527) at a concentration of ^{2.5x10 6 /ml and transfected.} In addition, enhancers (enhancer, Thermo Fisher; Cat.# A14524) was added to the transfected cells and _{cultured for 7 days at 37° C., CO 2} 8%, 125 rpm in a stirred incubator.

Thereafter, the supernatant of the culture medium was separated and reacted with kappa selection beads (select bead, GE Healthcare; Cat. # 17-5458-01) for 2 hours. Thereafter, the beads were washed with 10 ml of binding buffer, and 200 μl of elution buffer was added to the beads to separate and purify the CEACAM1 mutant protein from the beads (FIG. 1a).

After diluting 2.5 μg of each purified CEACAM1 mutant protein in 1,000 μl of PBS, 20 μl was dispensed into each well and reacted at 4° C. for 16 hours. Also, 1 µl of C25 After dilution in 1,000 μl of PBS, 25 μl was dispensed into each well and reacted at 37° C. for 1 hour. Then, each well was washed 3 times with a washing buffer in which 10 μl of Tween20 (Sigma-aldrich; Cat.# P9146) was diluted in 990 μl PBS. Thereafter, 1 μl of horse radish peroxidase (HRP)-conjugated human IgG (HRP-conjugated anti-human IgG: Sigma; Cat.# A0170) was diluted in 5000 μl of PBS and diluted in each well. 25 μl each and reacted at 37° C. for 1 hour.

After the reaction, the wells were washed 3 times with a washing buffer, and 25 μl of TMB solution (KPL; Cat.# 52-00-03) was added to each well to induce color development. Thereafter, 25 μl of 2M concentration of H ₂ SO4 was added to each well to stop the reaction, and absorbance was measured at a wavelength of 450 nm.

As a result, It has been shown that the N-domain and B-domain are essential sites for binding with full affinity. A1 and A2 were not shown to be required for direct binding. Therefore, it was shown that anti-CEACAM antibodies including C25 mainly bind to the N-domain of CEACAM1, and additionally require the B-domain to bind with full affinity ( FIG. 1b ).

Experimental example 1.2. CEACAM1 Protein and anti- CEACAM1 Confirmation of binding of antibodies

2.5 μg of recombinant CEACAM-1/CD66a protein (R&D systems; Cat. #2244-CM) was diluted in 10 ml of PBS, and then 100 μl was aliquoted into 96-well-plate (Nunc; Cat. # 467679) 4 The reaction was overnight at ℃ temperature. Thereafter, 300 μl of 1% (v/v) bovine serum albumin was added to each well, followed by reaction at 37° C. for 1 hour.

3 μg of C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 and C26 antibodies were each diluted in 1000 μl PBS. Each of the diluted antibodies was again serially diluted 6 times with PBS at a 1:1 volume ratio. 100 μl of each antibody diluted to 7 concentrations was dispensed into each well and reacted at 37° C. for 1 hour. Then, each well was washed 3 times with a washing buffer in which 10 μl of Tween20 (Sigma-aldrich; Cat.# P9146) was diluted in 990 μl PBS. Thereafter, 2 μl of HRP-conjugated human IgG was diluted in 10 ml of PBS, put into each well of 100 μl, and reacted for 1 hour.

After the reaction, the wells were washed 3 times with a washing buffer, and 100 μl of the TMB solution was added. It was added to each well to induce color development. Thereafter, 100 μl of 2M concentration of H ₂ SO ₄ was added to each well to stop the reaction, and absorbance was measured at a wavelength of 450 nm.

As a result, it was confirmed that the C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 or C26 antibody binds to the CEACAM1 protein ( FIG. 2 ).

Experimental Example 1.3. Confirmation of binding affinity between CEACAM1 and C25 expressed on the cell surface

Jurkat cells stably expressing CEACAM1 (Jurkat E6.1 (ATCC; TIB-152TM)) were transfected with CEACAM1 cDNA and treated with antibiotic G418 700 μg/ml. The selected cell line was selected with 2% (v/v ) After resuspending in DPBS with FBS (hereinafter, FACS buffer), centrifugation at 1,500 rpm, and resuspending ^{in FACS buffer so that the number of cells becomes 3x10 6} /ml, each U-bottom 96-well-plate 100 μl was put into each well.After that, the cells and culture solution of each well were recovered, centrifuged at 1,500 rpm, and the supernatant was discarded.The recovered cells were treated with human Fc block (BD Pharmingen; Cat. # 564220) solution. After resuspending in 50 μl of FACS buffer containing 0.5 μl, incubated at 4° C. for 15 minutes.

C25 or human IgG4 (Sigma; Cat.# I4639) in 50 μl of FACS buffer 20 μg/ml, 10 μg/ml, 5 μg/ml, 2.5 μg/ml, 1.25 μg/ml, 0.625 μg/ml, 0.3125 μg /ml, diluted to twice the concentration of 0.15625 μg/ml. 20 μg/ml, 10 μg/ml, 5 μg/ml, 2.5 μg/ml, 1.25 μg/ml, 0.625 μg/ml, and 20 μg/ml, 10 μg/ml, 5 μg/ml, After adjusting the concentrations to be 0.3125 μg/ml and 0.15625 μg/ml, the reaction was conducted at 4° C. for 1 hour and 30 minutes.

After the cells reacted with C25 were resuspended in FACS buffer, the washing process was repeated twice by centrifugation at 1,500 rpm. . Phycoerythrin (hereinafter, PE) a labeled goat anti-human ^{F (ab) 2 (Phycoerithrin-} conjugated goat anti-human F (ab) 2 (Sigma; Cat # P8047) for 1 in FACS buffer: 200 volume ratio After dilution, 100 μl was put into each well and reacted in the dark at 4° C. for 30 minutes.

The cells reacted with PE were recovered, resuspended in FACS buffer, centrifuged at 1,500 rpm, and the washing process discarding the supernatant was repeated twice. Thereafter, the cells were resuspended in 100 μl of fixation buffer (BD Cytofix™; Cat. # 554655) and incubated in the dark at 4° C. for 30 minutes.

The cells reacted with the fixation buffer were recovered, resuspended in FACS buffer, and centrifuged at 1,500 rpm to discard the supernatant, and the washing process was repeated twice. After the washed cells were resuspended in 200 μl of FACS buffer, the mean fluorescence intensity (MFI) of PE labeled with the cells was compared in a FACS LSR-Fortessa instrument. All FACS analyzes were performed using FlowJo software.

As a result, It was shown that the highest level of binding force was shown up to 5 μg/ml (MFI 1800 or higher), and then rapidly decreased from the concentration below that (FIG. 3).

Experimental example 1.4. port- CEACAM1 Determination of Antibody Affinity

Quantitative binding of C25 to CEACAM1 was ^{measured using Octet QK e} (Pall ForteBio). The antibody isolated and purified in Example 1. was diluted by half at a concentration of 400 nM six times, and the antibody at concentrations of 400 nM, 200 nM, 100 nM, 50 nM, 25 nM, 12.5 nM and 6.25 nM was mixed with Greiner 96. - Well-plate (Greiner, CAT. NO. 655209) was put in a row at a time of 200 μl, and the last well was put at a concentration of 0 nM. In another column, recombinant human CEACAM-1 (R&D Systems, CAT. NO. 2244-CM) was diluted to a concentration of 6.25 μg/μl, and 200 μl of each was added in a row.

Washing buffer, neutralization buffer and baseline buffer were diluted 10-fold with Reagent/Kinetics buffer (10X) (Fortebio, CAT. NO. 18-1092), and 200 μl of each column was added in a row, and regeneration buffer ( regeneration buffer) was added in a row by 200 μl. Prepare a separate Greiner 96-well-plate, put 200 μl of each well in the same number of wells as the number of biosensors to be used with Reagent/Kinetics buffer (1X) in a row, and Biosensors/Anti-His (His1K) (Fortebio, CAT. NO. 18 -5120) cassette was installed. Association and dissociation times were set to 300 seconds and 600 seconds, respectively, and KD values were measured.

As a result, it was confirmed that CEACAM1 had an affinity (KD) value of 1.82 nM to 39.0 nM ( FIG. 4 ).

Experimental example 2. Anti- CEACAM1 Confirmation of the physical properties of the antibody

Experimental Example 2.1. Isoelectric Point Identification of Anti-CEACAM1 Antibodies

20 ml of IEF anode buffer (50x) was mixed with 980 ml of deionized water (hereafter DW) to make 1xIEF anode buffer, and 20 ml of IEF cathode buffer pH3-10 (10x) was mixed with 180 ml of DW to make 1xIEF cathode buffer. 1xIEF anode buffer and 1xIEF cathode buffer were used after cooling to 4°C.

Using IEF gel (Invitrogen / pH 3-10 IEF gel, 1.0 mm x 10 well / EC6655BOX), 200 ml 1xIEF cathode buffer was filled in the upper chamber and 600 ml 1xIEF anode buffer was filled in the lower chamber. 15 μl of 20 μl of a mixture made by mixing 10 μl of C25 with a concentration of 1.12 mg/ml and 10 μl of IEF sample buffer (pH 3-10, 2x) was loaded, and as a marker, IEF Markers 3-10 (SERVA / 5 μl of 10 mg/mL / SERVA Liquid Mix, 39212.01) was used.

Electrophoresis was performed while changing the voltage over three steps to 100V: 1 hour, 200V: 1 hour, and 500V: 30 minutes, and fixed for 30 minutes using a 12% TCA solution. After fixation, the isoelectric point was confirmed after staining using Coomassie Blue R-250 Intron Biotechnology (IBS-BC006).

As a result, the actual value of the isoelectric point measured to optimize the buffer pH of the antibody was 8.0, which was slightly higher than the theoretical value of 7.76 (FIG. 5).

Experimental example 3. Section- CEACAM1 Antibody T cells Measuring Effect on Activation

Experimental Example 3.1. Measurement of T cell activation following anti-CEACAM1 antibody treatment

Jurkat-GFP/NFAT-luc (cells not expressing CEACAM1, cells overexpressing NFAT-luciferase reporter) or Jurkat-CCM1/NFAT-luc (cells overexpressing CEACAM1, cells overexpressing NFAT-luciferase reporter) cells were counted at 6x10 ⁵ cells per well After resuspending and putting in a 96-well-plate coated with 0.05 or 0.1 μg/ml of anti-CD3, each antibody at a concentration of 10 μg/ml and an anti- at a concentration of 1 μg/ml prepared in Example 1. CD28 was put together. Human IgG4 was used as a negative control.

After culturing for 6 hours, the cells were harvested, washed once with PBS, and lysed by adding 80 μl of passive lysis buffer. In a white 96-well-assay plate, 20 μl of cell lysate was placed in each well and the plate was placed in a luminometer instrument. After mounting the luciferase buffer (luciferase buffer) into the luminometer injector, 80 μl of each well was injected to measure luciferase activity.

As a result, in Jurkat-GFP/NFAT-luc, in which CCM1 is not expressed, there was no inhibitory effect on CCM1-dependent T cell suppression by C25, but in Jurkat-CCM1/NFAT-luc, TCR-induced NFAT activation by C25 was observed. was more than 2-fold at the concentrations of 0.05 and 0.1 μg/ml of anti-CD3 ( FIG. 6 ).

In addition, in the experimental group treated with the C25 clone, the NFAT-luc receptor activity was 1.5 times higher than that of the IgG4 treated group at a concentration of 0.1 μg/ml anti-CD3, and it was found that there was a statistical significance (FIG. 7).

Experimental example 4. By tissue in humans and monkeys CEACAM1 Expression confirmation

A 10 mM solution of EZ-Link™ Sulo-NHS-LC-LC-Biotin (ThermoFisher Scientific; Cat. # 21338) was prepared and 13.3 μl per 1 mg of C25 was added and biotinylated at 4° C. for 2 hours. Human and monkey TMA slides were deparaffinized in an oven at 60° C. for 1 hour. Xylene (Xylene 100%), alcohol (alcohol 90%), alcohol (alcohol-80%), alcohol (alcohol-DW) was gradually hydrated in the order.

For antigen retrieval, the TMA slides were treated in a constant temperature water bath containing 1.5 L Tris-EDTA pH 9.0 buffer and then reacted at 100° C. for 20 minutes. In order to prevent intracellular peroxidase activity, 100 μl of 3% hydrogen peroxide was treated and reacted for 6 minutes, and 100 μl of 5% (v/v) normal horse serum was treated and reacted for 30 minutes. .

The primary antibody (primary antibody, biotin-conjugated hIgG4 or C25; 1 mg/ml) was diluted at a 1:1 or 1:5 volume ratio and treated with 100 μl, followed by reaction at room temperature for 2 hours. After treatment with 100 μl of ABC reagent, it was reacted for 30 minutes. After treatment with DAB substrate kit (VECTOR LABORATORIES; Cat# SK-4100), the color was developed for 2 minutes, counterstained with hematoxylin, and analyzed. Since CEACAM1 expression in normal cells is very low, the antibody was used at a relatively high concentration.

The degree of C25 staining of Cynomolgus monkey normal tissues was similar to that of human normal tissues, and the expression level of CEACAM1 in normal tissues was very low. . As a control for C25, human IgG4 was used at the same concentration (Fig. 8b).

Experimental example 5. Para- CEACAM1 Identification of antibody cross-reactivity

Experimental example 5.1. human IgG Fab using an antibody CEACAM family Confirmation of cross-reaction between protein and anti-CEACAM1 antibody

Recombinant human CEACAM-1/CD66a protein (R&D systems; Cat.#2244-CM, HCCM1), Recombinant human CEACAM-5/CD66e protein (R&D systems; Cat.#4128-CM, HCCM5), Recombinant human CEACAM-6/ CD66c protein (R&D systems; Cat.#3934-CM, HCCM6), recombinant human CEACAM-3/CD66d protein (sino biological; Cat.# 11933-H08H, HCCM3), recombinant mouse PD-1 Fc chimeric protein (R&D systems; Cat. #1021-PD, mPD-1-Fc), Recombinant CEACAM1-Fc (IgG4) Protein (Mogam, Homemade, HCCM1-Fc), Recombinant Human CEACAM-1/CD66a Protein Bulk (R&D Systems; Cat. #2244) -CM, HCCM1 (bulk)) and mouse CEACAM1/CD66a protein (sino biological; Cat.# 50571-M08H, mouse CCM1) 2.5 μg were diluted in 10 ml PBS, and then 96-well-plate (Nunc; Cat. # 467679) by 100 μl and reacted at 4° C. overnight. Thereafter, 300 μl of 1% (v/v) bovine serum albumin was added to each well, followed by reaction at 37° C. for 1 hour.

3 μg of C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 and C26 antibodies were each diluted in 1000 μl PBS. 100 μl of the diluted antibodies were dispensed into each protein-coated well and reacted at 37° C. for 1 hour. Then, each well was washed 3 times with a washing buffer in which 10 μl of Tween20 (Sigma-aldrich; Cat.# P9146) was diluted in 990 μl PBS. Thereafter, 2 μl of HRP-conjugated human anti-IgG-Fab antibody (anti-human IgG Fab, Sigma cat.

After the reaction, the wells were washed 3 times with a washing buffer, and 100 μl of the TMB solution was added. It was added to each well to induce color development. Thereafter, 100 μl of 2M concentration of H ₂ SO ₄ was added to each well to stop the reaction, and absorbance was measured at a wavelength of 450 nm.

As a result, the C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 and C26 antibodies all showed high avidity to HCCM1, HCCM1 (bulk) and HCCM1-Fc, and the C17, C19, C22 antibodies The remaining anti-CEACAM1 antibodies except for HCCM3, HCCM5 and HCCM6 showed low binding affinity (FIG. 9). Through this, it was confirmed that the anti-CEACAM antibodies of the present invention specifically bind only to CEACAM1.

Experimental example 5.2. human IgG Fc using an antibody CEACAM family Protein and anti- CEACAM1 Identification of antibody cross-reactivity

Recombinant human CEACAM-1/CD66a protein (R&D systems; Cat.#2244-CM, HCCM1), Recombinant human CEACAM-5/CD66e protein (R&D systems; Cat.#4128-CM, HCCM5), Recombinant human CEACAM-6/ CD66c protein (R&D systems; Cat.#3934-CM, HCCM6), recombinant human CEACAM-3/CD66d protein (sino biological; Cat.# 11933-H08H, HCCM3), human B7-H5 / Gi24 / VISTA protein (sino biological) ; Cat. # 13482-H08H, HVISTA), recombinant human CEACAM-1/CD66a protein Bulk (R&D systems; Cat. #2244-CM, HCCM1 (bulk)), recombinant human CEACAM1-N-domain-Kappa protein (Mogam, After diluting 2.5 μg of self-made, HCCM1-Ndomain-kappa), and BSA protein in 10 ml of PBS, 100 μl of each was dispensed to a 96-well-plate and reacted at 4° C. overnight. Thereafter, 300 μl of 1% (v/v) bovine serum albumin was added to each well, followed by reaction at 37° C. for 1 hour.

3 μg of C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 and C26 antibodies were each diluted in 1000 μl PBS. 100 μl of the diluted antibodies were dispensed into each protein-coated well and reacted at 37° C. for 1 hour. Then, each well was washed 3 times with a washing buffer in which 10 μl of Tween20 (Sigma-aldrich; Cat.# P9146) was diluted in 990 μl PBS. Thereafter, 2 μl of HRP-conjugated human anti-IgG-Fc antibody (anti-human IgG Fc, Sigma cat.

After the reaction, the wells were washed 3 times with a washing buffer, and 100 μl of TMB solution was added to each well to induce color development. Thereafter, 100 μl of 2M concentration of H ₂ SO ₄ was added to each well to stop the reaction, and absorbance was measured at a wavelength of 450 nm.

As a result, the C15, C16, C17, C18, C19, C20, C21, C22, C23, C25 and C26 antibodies all showed high binding affinity to HCCM1, HCCM1 (bulk) and HCCM1-Ndomain-kappa, and C17, C19, Except for the C22 antibody, the remaining anti-CEACAM1 antibodies showed low binding affinity to HCCM3, HCCM5 and HCCM6 ( FIG. 10 ). Through this, it was confirmed that the anti-CEACAM antibodies of the present invention specifically bind only to CEACAM1.

Experimental example 5.3. expressed on the cell surface CEACAM family Confirmation of cross-reaction between protein and C25

10 μg of pEF1α-AcGFP-N1 vector (Clontech, Cat No. 631973), CEACAM1, CEACAM3, CEACAM5, CEACAM6, and CEACAM8 plasmid vectors were added to HEK293 cells as control vectors, and pulse voltage 1,100V, pulse voltage 1,100V, using the Neon transfection system. Transfection was carried out under the conditions of width 20ms and pulse number 2 . After 48 hours of transfection, GFP expression was confirmed under a fluorescence microscope, and cells were removed by treatment with 1 ml of TrypLE Express Solution (ThermoFisher Scientific; Cat. # 12605010), and DMEM (Gibco, Gibco, Cat No.11995-065) was diluted to 9 ml and centrifuged at 1,200 rpm for 5 minutes to remove the supernatant.

After washing once with PBS, the cells were resuspended in FACS buffer to a ^{concentration of 5x10 5} cells/100 μl. 1 μl of human Fc Block solution was added to each sample and reacted at 4° C. for 10 minutes. huIgG4 or C25 was treated at a concentration of 1 μg/5x10 ⁵ cells and reacted at 4° C. for 1 hour. After washing with FACS buffer, PE-labeled goat-anti-huIgG4 antibody was diluted 1:200 in FACS buffer, and 100 μl of each sample was added and reacted at 4° C. for 30 minutes. After filling up to 200 μl of FACS buffer, centrifugation was performed at 1,200 rpm for 5 minutes to remove the supernatant. 300 μl of fixation buffer was added and the cells were resuspended. Cells expressing GFP were selected in the FACS LSR-Fortessa equipment, and the expression was confirmed with a specific antibody for each CEACAM member according to the CEACAM member (Table 3). In addition, the binding of C25 was confirmed by PE fluorescence channel and analyzed using FlowJo software.

Kinds form substance name where to get it CEACAM1 cDNA clone CEACAM1 R&D Systems, RDC0951 isotype MouseIgG1 Isotype Control PE R&D Systems, IC002P Anti-CEACAM1 antibody Human CEACAM1/CD66a PEconjugated Antibody R&D Systems, FAB2244P CEACAM3 cDNA clone CEACAM3-GFP Origene, RG217469 isotype Sheep IgG R&D systems, 5-001-A Anti-CEACAM3 antibody HUMAN CEACAM-3/CD66d Antibody R&D systems, AF4166P secondary antibody Donkey Anti-Sheep IgG (H+L) Phycoerythrin R&D Systems, F0126 CEACAM5 cDNA clone CEACAM5-GFP Origene, RG206434 isotype MouseIgG2a Isotype Control PE R&D Systems, IC003P Anti-CEACAM5 antibody HUMAN CEACAM-5/CD66e PE-conjugated Antibody R&D systems, FAB41281P CEACAM6 cDNA clone CEACAM6-GFP Origene, RG202454 isotype Mouse IgG1 K Isotype Control PE eBioscience, 12-4714-82 Anti-CEACAM6 antibody Human CD66c-PE eBioscience, 12-0667-42 CEACAM8 cDNA clone CEACAM8 Origene/RG204740 isotype MouseIgG1 Isotype Control PE R&D Systems, IC002P Anti-CEACAM8 antibody Human CEACAM8 PE-conjugated Antibody R&D systems/FAB4246P

As a result, C25 was uniquely bound to CEACAM1 in the CEACAM member to which CEACAM1 belongs ( FIG. 11 ).

In addition, 10 μg of each control vector, Cynomolgus CEACAM1 plasmid vector, and human CEACAM1 plasmid vector was put into HEK293 cells and transfected under the conditions of pulse voltage 1,100V, pulse width 20ms and pulse number 2 using the Neon transfection system. After 48 hours of transfection, GFP expression was confirmed under a fluorescence microscope, the cells were removed by treatment with TrypLE Express solution, and the reaction was stopped by transferring to FACS buffer.

After washing once with PBS, the cells were resuspended in FACS buffer to a ^{concentration of 5x10 5} cells/100 μl. 1 μl of human Fc Block solution was added per sample and reacted at 4° C. for 10 minutes. Human IgG4 or C25 ^{was treated at a concentration of 1 μg/5} ×10 5 cells and reacted at 4° C. for 1 hour. After washing with FACS buffer, PE-labeled goat-anti-huIgG4 antibody was diluted 1:200 in FACS buffer, 100 μl each, and reacted at 4° C. for 30 minutes. After filling up to 200 μl of FACS buffer, centrifugation was performed at 1,200 rpm for 5 minutes to remove the supernatant. Cells were resuspended in 300 μl of fixation buffer. Cells expressing GFP were selected in the FACS LSR-Fortessa equipment, and the expression was confirmed with a specific antibody for each CEACAM member according to the CEACAM member. In addition, binding of C25 was confirmed by PE fluorescence channel and analyzed using FlowJo software.

As a result, it was confirmed that C25 recognized not only human CEACAM1 but also monkey (Cynomolgus) CEACAM1 ( FIG. 12 ).

Experimental Example 6. Confirmation of anti-cancer effect of anti-CEACAM1 antibody

Cancer cells (MKN45: JCRB Cell Bank; Cat.# JCRB0254;, MKN1:JCRB Cell Bank; Cat.# JCRB0252) were resuspended in RPMI 1640 medium (ThermoFisher Scientific; Cat.# 11875093) at a concentration of 1x104/200 μl and 96- Well-Put 200 μl into each well of the plate and incubated overnight at _{37° C. under 5% CO 2 conditions.} Non-conjugated cells were removed together with the medium, and TALL-104 (ATCC; Cat.#CRL-11386TM) or NK92MI (ATCC; Cat.#CRL-2408TM) cells were treated in various ratios (0:1, 0.1:1, 1:1, 10:1). At this time, C25 was put together in each well at a concentration of 10 μg/ml. As a control, huIgG4 was treated in the same way.

After co-culture for 6 hours, non-conjugated lysed cells were removed together with the medium, and Cell Titer 96 Aqueous One Solution (Promega; Cat.# G3582), an MTS assay reagent, was diluted 1:4 with RPMI 1640 medium. 200 μl of the diluted solution was added to each well and incubated for 3 hours in the dark. Thereafter, the O.D value of each sample was measured in a spectrophotometer with a wavelength of 490 nm, and the measured value was analyzed using the SoftMax Pro 5.4.1 program.

As a result, when the anticancer effect by CTL (Fig. 13a: TALL-104) or NK (Fig. 13b: NK-92MI) cells was confirmed as a method of confirming the in vitro efficacy of C25, CEACAM1 was expressed at a high level. In the case of the MKN45 gastric cancer cell line, C25 increased the anticancer immune response of CTLs and natural killer cells, whereas the MKN1 gastric cancer cell line in which CEACAM1 was not expressed at all did not show any anticancer effect ( FIGS. 13a and 13b ).

<110> Mogam Institute for Biomedical Research <120> ANTI-CEACAM1 ANTIBODY AND USE THEREOF <130> FPD/201710-0068 <160> 130 <170> KoPatentIn 3.0 <210> 1 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 1 Ser Ser Asn Ile Gly Asn Asn Tyr 1 5 <210> 2 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 2 Ser Ser Ser Asn Ile Gly Asn Asn Tyr 1 5 <210> 3 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 3 Ser Ser Asn Ile Gly Ser Asn Thr 1 5 <210> 4 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 4 Ser Ser Asn Ile Gly Asn Asn Ala 1 5 <210> 5 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 5 Ser Ser Asn Ile Gly Ser Asn Ala 1 5 <210> 6 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 6 Ser Ser Asn Ile Gly Ser Asn Tyr 1 5 <210> 7 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 7 Ser Ser Asn Ile Gly Ser Asn Asn 1 5 <210> 8 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VL) <400> 8 Ser Ser Asn Ile Gly Asn Asn 1 5 <210> 9 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 9 Ala Asp Ser Lys Arg Pro 1 5 <210> 10 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 10 Ala Asp Ser Arg Arg Pro 1 5 <210> 11 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 11 Ala Asp Ser Lys Arg Leu 1 5 <210> 12 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 12 Ala Asn Ser Asn Arg Pro 1 5 <210> 13 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 13 Ala Asp Asn Asn Arg Pro 1 5 <210> 14 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 14 Ala Asn Ser His Arg Pro 1 5 <210> 15 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 15 Ala Asn Ser His Arg Pro 1 5 <210> 16 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VL) <400> 16 Ser Asn Ser His Arg Pro 1 5 <210> 17 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 17 Gly Ala Trp Asp Leu Ser Leu Asn Gly Tyr Val 1 5 10 <210> 18 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 18 Gly Ala Trp Asp Val Ser His Asn Gly Tyr Val 1 5 10 <210> 19 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 19 Gly Ala Trp Asp Gln Ser Leu Asn Gly Tyr Val 1 5 10 <210> 20 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 20 Gly Ala Trp Asp Ser Met Gly Asn Gly Tyr Val 1 5 10 <210> 21 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 21 Gly Ala Trp Asp Ala Ser Tyr Asn Gly Tyr Val 1 5 10 <210> 22 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 22 Gly Ala Trp Asp Gly Arg Leu Asn Gly Tyr Val 1 5 10 <210> 23 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 23 Gly Ala Trp Asp Ala Ser Leu Asn Gly Tyr Val 1 5 10 <210> 24 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 24 Gly Thr Trp Asp Ala Ser Leu Ser Ala Tyr Val 1 5 10 <210> 25 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 25 Gly Thr Trp Asp Tyr Ser Leu Ser Gly Tyr Val 1 5 10 <210> 26 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 26 Gly Ser Trp Asp Asp Ser Leu Asn Ala Tyr Val 1 5 10 <210> 27 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 27 Ala Ala Trp Asp Ser Ser Leu Asn Gly Tyr Val 1 5 10 <210> 28 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 28 Gly Ser Trp Asp Ser Ser Leu Asn Ala Tyr Val 1 5 10 <210> 29 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VL) <400> 29 Gly Ala Trp Asp Tyr Ser Leu Ser Gly Tyr Val 1 5 10 <210> 30 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 30 Gly Phe Thr Phe Ser Asn Tyr Ala 1 5 <210> 31 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 31 Gly Phe Asn Phe Ser Asn Tyr Ala 1 5 <210> 32 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 32 Gly Phe Thr Phe Ser Ser Tyr Ser 1 5 <210> 33 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 33 Gly Phe Thr Phe Ser Asn Tyr Ser 1 5 <210> 34 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 34 Gly Phe Thr Phe Ser Asp Tyr Ser 1 5 <210> 35 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 35 Gly Phe Thr Phe Ser Asn Tyr Asp 1 5 <210> 36 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 36 Gly Phe Thr Phe Ser Gly Tyr Ala 1 5 <210> 37 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 37 Gly Phe Thr Phe Ser Asp Tyr Asp 1 5 <210> 38 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR1 (VH) <400> 38 Gly Phe Thr Phe Ser Gly Tyr Asp 1 5 <210> 39 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 39 Ile Ser His Gly Gly Gly Ser Ile 1 5 <210> 40 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 40 Ile Ser Pro Asn Gly Gly Asn Lys 1 5 <210> 41 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 41 Ile Ser Ser Asp Gly Gly Ser Lys 1 5 <210> 42 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 42 Ile Tyr Pro Asp Asp Gly Asn Thr 1 5 <210> 43 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 43 Ile Ser His Ser Ser Gly Ser Lys 1 5 <210> 44 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 44 Ile Tyr His Asp Gly Gly Ser Thr 1 5 <210> 45 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 45 Ile Tyr Ser Gly Ser Ser Ser Lys 1 5 <210> 46 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR2 (VH) <400> 46 Ile Ser Tyr Gly Gly Gly Ser Ile 1 5 <210> 47 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 47 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Thr Phe Asp Tyr 1 5 10 <210> 48 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 48 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Leu Phe Asp Tyr 1 5 10 <210> 49 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 49 Ala Lys Asp Pro Tyr Asn Ile Tyr Gln Pro Leu Phe Asp Tyr 1 5 10 <210> 50 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 50 Ala Arg Asp Pro Arg Lys His Val Asp Arg Tyr Phe Asp Tyr 1 5 10 <210> 51 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 51 Ala Arg Gly Ser Ile Trp Trp Leu Ser Leu Ile Pro Ser Ser Tyr Asn 1 5 10 15 Ala Met Asp Val 20 <210> 52 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 52 Ala Arg Asp Pro Leu Pro Cys Leu Ile Pro Lys Cys Ser Tyr Tyr Tyr 1 5 10 15 Ala Met Asp Val 20 <210> 53 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 53 Ala Arg Val Thr Val Leu Cys Thr Thr Tyr Gly Cys Ser Ser Tyr Asp 1 5 10 15 Gly Met Asp Val 20 <210> 54 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 54 Ala Lys Ala Pro Leu Pro Phe Tyr Phe Arg Pro Lys Ser Tyr Tyr Tyr 1 5 10 15 Ala Met Asp Val 20 <210> 55 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of CDR3 (VH) <400> 55 Ala Lys Asp Arg Leu Pro Gln Lys Ala Val Arg His Ser Tyr Ala Asn 1 5 10 15 Gly Met Asp Val 20 <210> 56 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 56 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Leu Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 57 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 57 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatt tgagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 58 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 58 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Val Ser His 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 59 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 59 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatg ttagccataa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 60 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 60 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Gln Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 61 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 61 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatc agagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 62 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 62 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ser Met Gly 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 63 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 63 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatt cgatgggtaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 64 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 64 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Leu Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 65 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 65 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta ggcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatc tgagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 66 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 66 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Tyr 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 67 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 67 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta ggcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccattag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatg ctagctataa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 68 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 68 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Leu Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Gly Arg Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 69 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 69 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggctaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatg gtcgtctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 70 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 70 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 71 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 71 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc caatattggc aataattatg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagta agcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatg ctagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 72 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 72 Gln Ser Val Leu Thr Gln Pro Leu Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Glu Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ala Ser Leu 85 90 95 Ser Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 73 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 73 cagtctgtgc tgactcagcc actctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc aataattatg tcaactggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctaatagta atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggagg aggctgatta ttactgtggt acttgggatg ctagcctgag tgcttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 74 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 74 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Thr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Asn Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Tyr Ser Leu 85 90 95 Ser Gly Tyr Val Leu Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 75 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 75 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc agtaatactg tctcctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgataata atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt acttgggatt atagcctgag tggttatgtc 300 ttaggcggag gcaccaagct gaccgtccta ggt 333 <210> 76 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 76 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Ala Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 77 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 77 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc aataatgctg tcaactggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctaatagtc atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt gcttgggatg ctagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 78 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 78 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Pro Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Ala Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Asp Ser Leu 85 90 95 Asn Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 79 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 79 cagtctgtgc tgactcagcc accctcagcg cctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc agtaatgctg tcacctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagtc atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt tcttgggatg atagcctgaa tgcttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 80 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 80 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Tyr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ser Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Ser Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 81 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 81 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtactg gctcttcatc taatattggc agtaattatg tcaactggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat tctaatagtc atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtgct gcttgggatt ctagcctgaa tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 82 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 82 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Asn Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Ser Ser Leu 85 90 95 Asn Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 83 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 83 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc agtaataatg tcacctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctaatagtc atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggatg aggctgatta ttactgtggt tcttgggatt ctagcctgaa tgcttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 84 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VL) <400> 84 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Tyr Ser Leu 85 90 95 Ser Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 <210> 85 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VL) <400> 85 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgtagtg gctcttcatc taatattggc aataattatg tcacctggta ccagcagctc 120 ccaggaacgg cccccaaact cctcatctat gctgatagtc atcggccaag cggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240 tccgaggacg aggctgatta ttactgtggt gcttgggatt atagcctgag tggttatgtc 300 ttcggcggag gcaccaagct gaccgtccta ggt 333 <210> 86 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 86 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Thr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 87 <211> 363 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 87 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc aattatgcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtg atctctcatg gtggtggtag tatatattac 180 gctgattctg taaaaggtcg gctcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagatcct 300 actaaggggt atgctcctac tttcgactac tggggccagg gtacactggt caccgtgagc 360 tca 363 <210> 88 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 88 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Leu Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 89 <211> 363 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 89 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc aattatgcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtg atctctcatg gtggtggtag tatatattac 180 gctgattctg taaaaggtcg gctcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagatcct 300 actaaggggt atgctccttt gttcgactac tggggccagg gtacactggt caccgtgagc 360 tca 363 <210> 90 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 90 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Thr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 91 <211> 363 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 91 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caactttagc aattatgcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtg atctctcatg gtggtggtag tatatattac 180 gctgattctg taaaaggtcg gctcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagatcct 300 actaaggggt atgctcctac tttcgattac tggggccagg gtacactggt caccgtgagc 360 tca 363 <210> 92 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 92 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ser Ile Ser Pro Asn Gly Gly Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Gly Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Pro Tyr Asn Ile Tyr Gln Pro Leu Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 93 <211> 362 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 93 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag ctctggattc acctttagca gttattctat gagctgggtc cgccaggctc 120 cagggaaggg gctggagtgg gtctcatcga tctctcctaa tggtggtaat aaatattacg 180 ctgattctgt aaaaggtcgg ttcaccatct ccagagacaa ttccaagaac acgctgtatc 240 tgcaaatgaa cagcctggga gccgaggaca cggccgtgta ttactgtgcg aaagatcctt 300 ataatattta tcagcctttg ttcgactact ggggccaggg tacactggtc accgtgagct 360 ca 362 <210> 94 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 94 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Ser Asp Gly Gly Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Arg Lys His Val Asp Arg Tyr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 95 <211> 363 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 95 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc aattattcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagcg atctcttctg atggtggtag taaatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagatcct 300 cgtaagcatg tggatcgtta tttcgactac tggggccagg gtacactggt caccgtgagc 360 tca 363 <210> 96 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 96 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Tyr Pro Asp Asp Gly Asn Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ser Ile Trp Trp Leu Ser Leu Ile Pro Ser Ser Tyr Asn 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Ala Val Ser Ser 115 120 125 <210> 97 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 97 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc gattattcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtg atctatcctg atgatggtaa tacatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagaggtagt 300 atttggtggc tgtctttgat tccttcttct tataatgcta tggacgtctg gggccagggt 360 acactggtca ccgtgagctc a 381 <210> 98 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 98 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Gly Ile Ser His Ser Ser Gly Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Leu Pro Cys Leu Ile Pro Lys Cys Ser Tyr Tyr Tyr 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <210> 99 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 99 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc aattatgata tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcaggg atctctcata gtagtggtag taaatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagatcct 300 cttccgtgtc ttattcctaa gtgttcttat tattatgcta tggacgtctg gggccagggt 360 acactggtca ccgtgagctc a 381 <210> 100 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 100 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Gly Ile Tyr His Asp Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Thr Val Leu Cys Thr Thr Tyr Gly Cys Ser Ser Tyr Asp 100 105 110 Gly Met Asp Val Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <210> 101 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 101 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc ggttatgcta tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcaggg atctatcatg atggtggtag tacatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gagagttact 300 gttctgtgta cgacgtatgg ttgttcttct tatgatggta tggacgtctg gggccagggt 360 acactggtca ccgtgagctc a 381 <210> 102 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 102 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Met Ile Tyr Ser Gly Ser Ser Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Ala Pro Leu Pro Phe Tyr Phe Arg Pro Lys Ser Tyr Tyr Tyr 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <210> 103 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 103 gaggtgcagc tgttggagtc cgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc gattatgata tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcaatg atctattctg gtagtagtag taaatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gaaagctcct 300 cttccgtttt attttcggcc taagtcttat tattatgcta tggacgtctg gggccagggt 360 acactggtca ccgtgagctc a 381 <210> 104 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of variable region (VH) <400> 104 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Trp Ile Ser Tyr Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Arg Leu Pro Gln Lys Ala Val Arg His Ser Tyr Ala Asn 100 105 110 Gly Met Asp Val Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <210> 105 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide sequence for anti-CEACAM1 antibody of variable region (VH) <400> 105 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc ggttatgata tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcatgg atctcttatg gtggtggtag tatatattac 180 gctgattctg taaaaggtcg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gaaagatcgt 300 cttcctcaga aggctgtgcg gcattcttat gctaatggta tggacgtctg gggccagggt 360 acactggtca ccgtgagctc a 381 <210> 106 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 106 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Leu Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 107 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 107 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Val Ser His 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 108 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 108 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Gln Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 109 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 109 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ser Met Gly 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 110 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 110 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Leu Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 111 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 111 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Tyr 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 112 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 112 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Leu Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Gly Arg Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Arg Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Glu His Arg Gly Lys 195 200 205 Arg Gln Trp Pro Thr Glu Cys 210 215 <210> 113 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 113 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Arg Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Glu His Arg Gly Lys 195 200 205 Arg Gln Trp Pro Thr Glu Cys 210 215 <210> 114 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 114 Gln Ser Val Leu Thr Gln Pro Leu Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Glu Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ala Ser Leu 85 90 95 Ser Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 115 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 115 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Thr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Asn Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Tyr Ser Leu 85 90 95 Ser Gly Tyr Val Leu Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 116 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 116 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Ala Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Ala Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 117 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 117 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Pro Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Ala Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Asp Ser Leu 85 90 95 Asn Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 118 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 118 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Tyr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ser Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Ser Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 119 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 119 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 Asn Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asn Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Ser Ser Leu 85 90 95 Asn Ala Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 120 <211> 215 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of light chain <400> 120 Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 1 5 10 15 Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 25 30 Tyr Val Thr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Ala Asp Ser His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Tyr Ser Leu 85 90 95 Ser Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 100 105 110 Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Ser Ser Glu Glu 115 120 125 Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140 Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 145 150 155 160 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 165 170 175 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 180 185 190 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 Thr Val Ala Pro Thr Glu Cys 210 215 <210> 121 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 121 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Thr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 210 215 220 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445 <210> 122 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 122 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Leu Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 210 215 220 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445 <210> 123 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 123 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Phe Ser Asn Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser His Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Thr Lys Gly Tyr Ala Pro Thr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 210 215 220 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445 <210> 124 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 124 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ser Ile Ser Pro Asn Gly Gly Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Gly Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Pro Tyr Asn Ile Tyr Gln Pro Leu Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 210 215 220 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445 <210> 125 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 125 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Ser Asp Gly Gly Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Arg Lys His Val Asp Arg Tyr Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 130 135 140 Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 195 200 205 Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 210 215 220 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445 <210> 126 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 126 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Tyr Pro Asp Asp Gly Asn Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ser Ile Trp Trp Leu Ser Leu Ile Pro Ser Ser Tyr Asn 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Ala Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 130 135 140 Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 195 200 205 Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 325 330 335 Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Leu Gly Lys 450 <210> 127 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 127 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Gly Ile Ser His Ser Ser Gly Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Pro Leu Pro Cys Leu Ile Pro Lys Cys Ser Tyr Tyr Tyr 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 130 135 140 Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 195 200 205 Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 325 330 335 Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Leu Gly Lys 450 <210> 128 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 128 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Gly Ile Tyr His Asp Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Thr Val Leu Cys Thr Thr Tyr Gly Cys Ser Ser Tyr Asp 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 130 135 140 Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 195 200 205 Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 325 330 335 Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Leu Gly Lys 450 <210> 129 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 129 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Met Ile Tyr Ser Gly Ser Ser Ser Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Ala Pro Leu Pro Phe Tyr Phe Arg Pro Lys Ser Tyr Tyr Tyr 100 105 110 Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 130 135 140 Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 195 200 205 Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 325 330 335 Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Leu Gly Lys 450 <210> 130 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence for anti-CEACAM1 antibody of heavy chain <400> 130 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Tyr 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Trp Ile Ser Tyr Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Arg Leu Pro Gln Lys Ala Val Arg His Ser Tyr Ala Asn 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 115 120 125 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 130 135 140 Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 145 150 155 160 Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 165 170 175 Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 180 185 190 Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 195 200 205 Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 210 215 220 Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 225 230 235 240 Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 245 250 255 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 260 265 270 Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 275 280 285 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 290 295 300 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 305 310 315 320 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 325 330 335 Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 340 345 350 Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn 355 360 365 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 370 375 380 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 385 390 395 400 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 405 410 415 Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 420 425 430 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 435 440 445 Ser Leu Ser Leu Gly Lys 450

Claims (45)

delete Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 17, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 3. The method of claim 2,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 56 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 18, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 5. The method of claim 4,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 58 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 19, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 7. The method of claim 6,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 60 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 20, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 9. The method of claim 8,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 62 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 17, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 11. The method of claim 10,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 21, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 13. The method of claim 12,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 66 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 11, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 22, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 15. The method of claim 14,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 68 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 17, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising:
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 17. The method of claim 16,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 88, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 10, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 17, amino acid sequence shown in SEQ ID NO: 31 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 19. The method of claim 18,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 64 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 90, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 2, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 12, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 24, amino acid sequence shown in SEQ ID NO: 32 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 40;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 21. The method of claim 20,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 72 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 92, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 3, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 13, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 25, amino acid sequence shown in SEQ ID NO: 33 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising:
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 23. The method of claim 22,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 74 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 94, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 4, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 14, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 23, amino acid sequence shown in SEQ ID NO: 34 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising:
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 25. The method of claim 24,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 76 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 96, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 5, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 15, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 26, amino acid sequence shown in SEQ ID NO: 35 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising:
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 27. The method of claim 26,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 78 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 98, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 6, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 16, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 27, amino acid sequence shown in SEQ ID NO: 36 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 44;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 29. The method of claim 28,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 80 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 100, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 7, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 14, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 28, amino acid sequence shown in SEQ ID NO: 37 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 45;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 31. The method of claim 30,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 82 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 102, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 8, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 15, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 29, amino acid sequence shown in SEQ ID NO: 38 An anti-CEACAM1 antibody or fragment thereof, comprising a heavy chain CDR1 comprising:
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 33. The method of claim 32,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 84 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 104, anti-CEACAM1 antibody or fragment thereof. Light chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, light chain CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9, light chain CDR3 comprising the amino acid sequence shown in SEQ ID NO: 23, amino acid sequence shown in SEQ ID NO: 30 An anti-CEACAM1 antibody or fragment thereof comprising a heavy chain CDR1 comprising: a heavy chain CDR1 comprising the amino acid sequence shown in SEQ ID NO: 39;
The fragment is an anti-CEACAM1 antibody or fragment thereof, characterized in that any one selected from the group consisting of Fab, scFv, F(ab) ^{2 and Fv.} 35. The method of claim 34,
The antibody is characterized in that it comprises a light chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 70 and a heavy chain variable domain comprising the amino acid sequence shown in SEQ ID NO: 86, anti-CEACAM1 antibody or fragment thereof. 36. An anticancer agent comprising the anti-CEACAM1 antibody or fragment thereof of any one of claims 2 to 35 as an active ingredient. 37. The method of claim 36,
The cancer is characterized in that any one selected from the group consisting of pancreatic cancer, melanoma, lung cancer and myeloma, anticancer agent. 36. An anticancer adjuvant comprising the anti-CEACAM1 antibody or fragment thereof of any one of claims 2 to 35 as an active ingredient. A composition for treating cancer comprising the anticancer adjuvant of claim 38 and a cell therapy agent. 40. The method of claim 39,
The cell therapy agent, characterized in that the cytotoxic T cells or natural killer cells, cancer treatment composition. 36. A method for treating cancer comprising administering to a non-human subject the lymphocytes contacted with the anti-CEACAM1 antibody or fragment thereof of any one of claims 2-35. 42. The method of claim 41,
The method for treating cancer, characterized in that the lymphocytes include at least one of cytotoxic T cells and natural killer cells. 42. The method of claim 41,
Wherein the lymphocytes are obtained from individuals other than humans, cancer treatment method. 42. The method of claim 41,
The cancer is characterized in that any one selected from the group consisting of pancreatic cancer, melanoma, lung cancer and myeloma, cancer treatment method. 36. A method of inhibiting proliferation of CEACAM1-expressing tumor cells in a non-human subject, comprising contacting the CEACAM1-expressing tumor cells with the anti-CEACAM1 antibody or antibody fragment of any one of claims 2-35.

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