Individualized anti-cancer antibodies
The present invention relates to a method for producing patient specific anti-cancer antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies customized for the individual patient that can be used for therapeutic and diagnostic purposes. The invention further relates to the process by which the antibodies are made and to their methods of use. The antibodies can be made specifically for one tumor derived from a particular patient and are selected on the basis of their cancer cell cytotoxicity and simultaneous lack of toxicity for non-cancerous cells. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat tumor metastases. The anti-cancer antibodies can be conjugated to red blood cells obtained from that patient and re-infused for treatment of metastases based upon the recognition that metastatic cancers are usually well vascularized and the delivery of anti-cancer antibodies by red blood cells can have the effect of concentrating the antibodies at the site of the tumor.
1 . Anti-cancer antibodies or fragments thereof produced in accordance with a method for the selection of individually customized anti-cancer antibodies which are useful in treating a cancerous disease, said antibodies comprising:
a customized subset of antibodies or fragments thereof characterized as being cytotoxic against cells of a cancerous tissue, said subset being essentially benign to non-cancerous cells.
2 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through antibody dependent cellular toxicity.
3 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through complement dependent cellular toxicity.
4 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through catalyzing of the hydrolysis of cellular chemical bonds.
5 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through producing an immune response against putative cancer antigens residing on tumor cells.
6 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through targeting of cell membrane proteins to interfere with their function.
7 . The anti-cancer antibodies or fragments thereof in accordance with claim 1 wherein the cytotoxicity of said antibodies is mediated through production of a conformational change in a cellular protein effective to produce a signal to initiate cell-killing.
8 . The anti-cancer antibodies of claim 1 wherein:
said method of selection utilizes a tissue sample obtained from a particular individual containing cancerous and non-cancerous cells.
9 . Anti-cancer antibodies or fragments thereof wherein the antibody is selected from the group consisting of an 3BD-3, a 3BD-6, a 3BD-8, a 3BD-9, a 3BD-15, a 3BD-25, a 3BD-26 and a 3BD-27 monoclonal antibody.
10 . Anti-cancer antibodies or fragments thereof wherein the antibody is produced by a hybridoma cell line having an ATCC Accession Number selected from the group consisting of (______).
11 . Anti-cancer antibodies or fragments thereof wherein the antibody is selected from the group consisting of an 1LN-1, a 1LN-12, a 1LN-14, a 2LN-21, a 2LN-28, a 2LN-29, a 2LN-31, a 2LN-33, a 2LN-34 and a 2LN-35.
12 . Anti-cancer monoclonal antibodies or fragments thereof wherein the antibody is produced by a hybridoma cell line having an ATCC Accession Number selected from the group consisting of (______).