JPWO2019191120A5

JPWO2019191120A5 -

Info

Publication number: JPWO2019191120A5
Application number: JP2020551549A
Authority: JP
Publication date: 2022-05-11

Claims

Binding domain for T cell activation receptors,
Binding domain for tumor-related antigens,
Binding domains for immune checkpoint receptors, and
Binding domain for T cell co-stimulatory receptors,
Including
Here, the binding domain for the tumor-related antigen is not adjacent to the binding domain for the T cell co-stimulatory receptor.
Guidance and Navigation Control (GNC) protein.

The guidance and navigation control (GNC) protein of claim 1, wherein the binding domain to the T cell activating receptor is adjacent to the binding domain of the tumor-related antigen (TAA).

The guidance and navigation control (GNC) protein of claim 1, wherein the T cell activating receptor comprises CD3.

Immune checkpoint receptors include PD-L1, PD-1, TIGIT, TIM-3, LAG-3, CTLA4, BTLA, VISTA, PDL2, CD160, LOX-1, siglec-15, CD47, or a combination thereof. The guidance and navigation control (GNC) protein of claim 1, including.

The guidance and navigation control (GNC) protein of claim 1, wherein the T cell co-stimulatory receptor comprises 4-1BB, CD28, OX40, GITR, CD40L, ICOS, Light, CD27, CD30, or a combination thereof.

Tumor-related antigens are ROR1, CD19, EGRFVIII, BCMA, CD20, CD33, CD123, CD22, CD30, CEA, HER2, EGFR, LMP1, LMP2A, mesocellin, PSMA, EpCAM, glypican-3, gpA33, GD2, TROP2, or The Guidance and Navigation Control (GNC) Protein of Claim 1, comprising a combination thereof.

The tumor-related antigens are lung cancer cells, liver cancer cells, breast cancer cells, colon cancer cells, anal cancer cells, pancreatic cancer cells, bile sac cancer cells, bile duct cancer cells, head and neck cancer cells, and nasopharynx. Cancer cells, skin cancer cells, melanoma cells, ovarian cancer cells, prostate cancer cells, urinary tract cancer cells, lung cancer cells, non-small cell lung cancer cells, small cell lung cancer cells, brain tumor cells, glioma cells, neuroblastoma Cells, esophageal cancer cells, gastric cancer cells, liver cancer cells, kidney cancer cells, bladder cancer cells, cervical cancer cells, endometrial cancer cells, thyroid cancer cells, eye cancer cells, sarcoma The Guidance and Navigation Control (GNC) protein of claim 1, which is a receptor on cells, bone cancer cells, leukemia cells, myeloma cells, lymphoma cells, or combinations thereof.

The guidance and navigation control (GNC) protein of claim 1, wherein the protein is a triple or quadruplex specific antibody comprising an Fc domain.

The T cell activating receptor contains CD3, and the binding domain for CD3 is linked to the binding domain for tumor-related antigen (TAA) via a peptide linker to form a CD3-TAA pair, and the peptide linker is 100. The Guidance and Navigation Control (GNC) protein of claim 8 having a length not exceeding an amino acid.

The Guidance and Navigation Control (GNC) protein of claim 9, wherein the peptide linker has a length not exceeding 20 amino acids.

The Guidance and Navigation Control (GNC) protein of claim 9, wherein the peptide linker has a length not exceeding 10 amino acids.

The Guidance and Navigation Control (GNC) protein of claim 9, wherein the peptide linker has a length of about 2 to about 10 amino acids.

The Guidance and Navigation Control (GNC) protein of claim 9, wherein the tumor-related antigen comprises ROR1, CD19, or EGRFVIII.

The Guidance and Navigation Control (GNC) protein of claim 9, wherein the IgG Fc domain mediates the binding domain to the CD3-TAA pair and immune checkpoint receptors.

The guidance and navigation control (GNC) protein of claim 14, wherein the immune checkpoint receptor comprises PD-L1.

It has an N-terminal and a C-terminal, and in tandem from the N-terminal to the C-terminal,
Binding domain for CD3,
Binding domain for EGFRVIII,
IgG Fc domain,
Binding domain for PD-L1 and
The guidance and navigation control (GNC) protein of claim 9, which comprises a binding domain for 41-BB.

The Guidance and Navigation Control (GNC) protein of claim 16, comprising an amino acid sequence having a percentage homology to SEQ ID NOs: 80 and 82, wherein the percentage homology is not less than 98%.

It has an N-terminal and a C-terminal, and in tandem from the N-terminal to the C-terminal,
Binding domain for 4-1BB,
Binding domain for PD-L1,
IgG Fc domain,
Binding domain for ROR1 and
The Guidance and Navigation Control (GNC) protein of claim 9, which comprises a binding domain for CD3.

The Guidance and Navigation Control (GNC) protein of claim 18, which comprises an amino acid sequence having a percentage homology with SEQ ID NOs: 88 and 90, wherein the percentage homology is not less than 98%.

It has an N-terminal and a C-terminal, and in tandem from the N-terminal to the C-terminal,
Binding domain for CD3,
Binding domain for CD19,
IgG Fc domain,
Binding domain for PD-L1 and
The guidance and navigation control (GNC) protein of claim 9, which comprises a binding domain for 41-BB.

The Guidance and Navigation Control (GNC) protein of claim 20, comprising an amino acid sequence having a percentage homology to SEQ ID NOs: 104 and 106, wherein the percentage homology is not less than 98%.

Contains amino acid sequences having percentage homology to SEQ ID NOs: 50, 52, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, and 110, said. The GNC protein of claim 1, wherein the percentage homology is not less than 98%.

Nucleic acid encoding the GNC protein of claim 1.

Percentages for SEQ ID NOs: 49, 51, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, and 109 with percentage homology not less than 98% The nucleic acid of claim 23 having homology.

T cells with T cell activation receptors and T cell co-stimulatory receptors, and
The GNC protein of claim 1, which binds to T cells through interaction with T cell activating receptors, T cell co-stimulating receptors, or combinations thereof.
Cytotoxic cells, including.

A cancer cell having a tumor-related antigen, and the GNC protein according to claim 1, which is bound to the cancer cell through an interaction with the tumor-related antigen.
Including cancer cells.

T cells with T cell activation receptors and T cell co-stimulatory receptors,
Cancer cells having tumor-related antigens, and the GNC protein of claim 1,
Including
Here, the GNC protein binds to T cells via an interaction with a T cell activating receptor, a T cell co-stimulating receptor, or a combination thereof, and the GNC protein is associated with a tumor-related antigen. Binds to cancer cells through interactions,
Biological complex.

Claims 1, 9, 16, 18, or 20 GNC proteins, or 25 cytotoxic cells, or combinations thereof, and pharmaceutically acceptable carriers.
A pharmaceutical composition comprising.

A pharmaceutical composition comprising an effective amount of the pharmaceutical composition of claim 28 for the treatment of a subject having cancer.