KR910009284A - Chimeric Mouse-Human A10 Antibodies Specific to Human Tumor Cell Antigens - Google Patents

Abstract

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Description

Chimeric Mouse-Human A10 Antibodies Specific to Human Tumor Cell Antigens

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3 shows a schematic of the chain mammalian expression plasmid pING 2254 in chimeric mouse-human A10. The V region of the cDNA clone prA10-16 is treated as compatible with the eukaryotic expression plasmid pING2227. Plasmid pING2227 contains the following gene regulatory elements useful for expression in mammalian cells. 1) IgGH chain enhancer, 2) Abelson LTR promoter, 3) SV40 16S splice site, and 4) IgGH chain polyadenylation signal sequence, pING2227 also contains the entire human IgG1C region derived from pGNH-6. Liu, A. Y. et al., Proc. Natl, Acad. Sci., USA 84: 3439 (1987). pING2227 contains a neomycin phosphotransferase gene that allows for the selection of G418 in transgenic cells.

Claims (33)

A polynucleotide molecule comprising a variable region codine sequence of an immunoglobulin chain specific for an antigen bound by a murine A10 antibody. The molecule of claim 1 wherein the chain is a heavy chain. The molecule of claim 1, wherein the chain is a light chain. The molecule of claim 1, further comprising an additional sequence that at least partially coats the constant region of the human immunoglobulin chain and wherein the two sequences are in interoperable binding state. The molecule of claim 4, wherein the additional sequence is a CDNA sequence. The molecule of claim 1 which is in the form of recombinant DNA. The molecule of claim 6 which is in the form of double stranded DNA. The molecule of claim 7 which is an expression carrier. The molecule of claim 8, wherein the carrier is a plasmid. Prokaryotic host transformed with the molecule of claim 4. The host of claim 10 which is a bacterium. Eukaryotic host transfected with the molecule of claim 4. The host of claim 12, which is a yeast cell or a mammalian cell. A chain in a chimeric immunoglobulin characterized by containing at least some human constant regions and at least some variable regions specific for antigens bound by A10 murine monoclonal antibodies. A chimeric immunoglobulin light chain, characterized in that it contains at least some human constant regions and at least some variable regions specific for antigens bound by A10 murine monoclonal antibodies. A chimeric form characterized by each chain comprising two light chains and two heavy chains containing at least some human constant regions and at least some variable regions specific for the antigen bound by the A10 murine monoclonal antibody Antibody molecule or fragment or derivative thereof. The antibody, fragment or derivative of claim 16 which is in a detectably labeled form. The antibody, fragment or derivative of claim 17 wherein the label is a radionuclide. The antibody, fragment or derivative of claim 16 conjugated to a cytotoxic drug. The antibody, fragment or derivative of claim 16 conjugated to a cytotoxic protein. The antibody, fragment or derivative of claim 16 immobilized on a solid phase. at least some human constant regions, characterized by (a) culturing a host capable of expressing light chains under culture conditions, (b) expressing heavy chains, and (c) recovering heavy chains from the culture, and A method for producing a chimeric immunoglobulin heavy chain having at least some variable regions specific for antigens bound by A10 murine monoclonal antibodies. at least a portion of the human constant region, characterized by (a) culturing a host capable of expressing light chains under culture conditions, (b) expressing light chains in the light chain, and (c) recovering light chains from the culture. And a method for preparing a chain in a chimeric immunoglobulin having at least some variable regions specific for an antigen bound by an A10 murine monoclonal antibody. (a) culturing a host capable of expressing light chains under culture conditions, expressing light chains, recovering light chains from the culture, and (b) separately forming a host capable of exposing heavy chains under culture conditions. Each chain is characterized by culturing, expressing a heavy chain, recovering the heavy chain from the culture, and (c) combining the recovered heavy and light chains to produce a chimeric immunoglobulin, fragment or derivative. A method of making a chimeric immunoglobulin, fragment or derivative comprising heavy and light chains having at least some human constant regions and at least some variable regions specific for antigens bound by A10 murine monoclonal antibodies. (a) a host capable of expressing a heavy chain and a host capable of expressing a light chain are cultured together under culture conditions, (b) expressing a heavy chain and a light chain, and (c) binding a heavy chain and a light chain. To a chimeric immunoglobulin, fragment or derivative, and (d) recovering the chimeric immunoglobulin, fragment or derivative from the culture, wherein each chain is subjected to at least some human constant region and A10 murine monoclonal antibody. A method for producing a chimeric immunoglobulin, fragment or derivative containing heavy and light chains having at least some variable regions specific for antigens bound by the same. (a) a host capable of expressing heavy chains and light chains is cultured under culture conditions, (b) expresses a chimeric immunoglobulin, fragment or derivative, and (c) a chimeric immunoglobulin, fragment or derivative in culture A chimeric immunoglobulin containing heavy chains and light chains having at least some human constant regions of each chain and at least some variable regions specific for antigens bound by A10 murine monoclonal antibodies, characterized in that Method for the preparation of fragments or derivatives. 27. The method of any one of claims 22-26, wherein the host is a prokaryote. 27. The method of any one of claims 22-26, wherein the host is a eukaryote. (a) contacting a sample with the antibody, fragment or derivative of claims 16, 17, 18 or 21, and (b) detecting the antigen by binding detection of the antibody, fragment or derivative. An immunoassay for detecting antigens capable of binding to A10 murine monoclonal antibodies. An antigen detection shaping method capable of binding to an A10 murine monoclonal antibody in an animal, characterized by contacting an animal with (a) the labeled antibody, fragment or derivative of claim 17 and (b) an antigen. A method of killing a cell carrying an antigen capable of binding to an A10 murine monoclonal antibody characterized by (a) delivering the antibody, fragment or derivative of any one of claims 16 to 20 to the cell and (b) killing it. . 32. The method of claim 31, wherein killing occurs by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, radiation cytotoxicity, cytotoxic drug action or protein toxin action. An effective amount of the antibody, fragment or derivative of any one of claims 16-20, wherein the subject is thought to have a tumor that is thought to have a tumor bearing an antigen capable of binding to an A10 murine monoclonal antibody. ※ Note: The disclosure is based on the initial application.