Anti-cancer Antibodies Specific to Tumor-associated Antigens Expressed on All Epithelial Carcinomas

Inventors:    Magdalena Thurin

Tech ID:    TM-01RR

Description: Human tumors have been shown to accumulate large quantities of abnormal carbohydrate surface structures, which represent oncodevelopmentally regulated antigens. Specifically, carbohydrate structures expressed by human adenocarcinomas represent the blood group antigens ( Le^a, Le^b, LeX, LeY, H-2, B-1, B-2 ). GD2 and GD3 gangliosides have been identified to be specifically expressed in human melanoma. Wistar scientists have isolated numerous antibodies secreted by hybridomas derived from the immunization of mice with live tumor cells. Hybridomas with restricted reactivities were selected, subcloned and the secreted antibodies have been tested on a variety of tumor and normal cells. The antibodies demonstrate extreme specificity to tumor-associated antigens expressed on all epithelial carcinomas (breast cancer, prostate cancer, gastrointestinal cancer and lung cancer) and neuroectodermal tumors. The Wistar-developed antibodies described herein provide excellent tools for the identification of tumor-associated antigens and blood group antigens.

Antibodies that bind to Lewis Blood Group Antigens

• Monoclonal Antibodies CO51.4, CO43.1, and CO51.3 are secreted by hybridomas derived from mice immunized with human colon carcinoma cells.

  Reactivities: Antibody CO51.4 is specific for the Lea oligosaccharide and antibody CO43.1 detects the Le^b oligosaccharide. Antibody CO51.3 is cross-reactive to both Le^a and Le^b antigens. Antibodies CO51.4, CO51.3 are of the IgG3 isotype. CO43.1 is of the IgM isotype.

  References:Blaszczyk, M, Hansson, GC, Karlsson, KA, Larson, G, Stromberg, N, Thurin, J, Herlyn,M, Steplewski, Z, and Koprowski, H. 1984. Lewis blood group antigens defined by monoclonal anti-colon carcinoma antibodies. Archives of Biochemistry and Biophysics, 233: 161-168, 1984.

  Brockhaus, Manfred, Magnani, John L., Herlyn, Meenhard, Blaszczyk, Magdalena, Steplewski, Zenon, Koprowski, Hilary, and Ginsburg, Victor. Monoclonal antibodies directed against the sugar sequence of lacto-N-fucopentaose III are obtained from mice immunized with human tumors. Archives of Biochemistry and Biophysics, 217:647-651, 1982.

  Intellectual Property Position: The utilization of antibodies CO51.4, CO43.1 and CO51.3 in an assay to detect Le^a and Le^b antigens is subject to the claims of US Patent No. 4,607,009, entitled "Lewis Blood Group Phenotype Assay."

• Monoclonal antibody BR-15-6-A is produced by hybridomas derived from mice immunized with human breast adenocarcinoma cells.

  Specificity: Antibody BR-15-6A is not cross-reactive; the antibody binds to human LeY blood group antigen.

  Reference(s): Rodeck, U, Herlyn, M, Leander, K, Borlinghaus, P, and Koprowski, H. A mucin containing the X, Y, and H type 2 carbohydrate determinants is shed by carcinoma cells. Hybridoma, 6:389-401, 1987.

• Monoclonal antibody PRD8 is produced by a hybridoma derived from mice immunized with human prostatic carcinoma cell line.

  Reactivity: The antibody binds to the type 2 H-2 determinant. Antibody PRD8 is of the IgM isotype.

  Reference(s): Lindgren, J, Blaszczyk, M, Atkinson, B, Steplewski, Z, and Koprowski, H. 1986. Monoclonal antibody-defined antigens of human prostate cancer cell line PC3. Cancer Immunology and Immunotherapy, 22:1-7.

• Antibody CO29-1 is produced by hybridomas derived from mice immunized with a primary human gastric adenocarcinoma cells. Antibody CO56-45 was secreted by hybridomas derived from mice immunized with a human rectal carcinoma cell line.

  Reactivity: Antibodies CO29-1 and CO-56-45 bind to human LeX blood group antigen.

  Reference(s): Brockhaus, M, Magnani, JL, Herlyn, M, Blaszczyk, M, Steplewski, Z, Koprowski, H and Ginsberg, V. 1982. Monoclonal antibodies directed against the sugar sequences of Lacto-N-frucopentaose III are obtained from mice immunized with human tumors. Archives of. Biochemistry and Biophysics, 217:647-651, 1982.

  Hansson, GC, Karlsson, KA, Larson, G, McKibbin, JM, Blaszczyk, M, Herlyn, Steplewski, Z and Koprowski. 1983. Mouse monoclonal antibodies against human cancer cells lines with specificities for blood group antigens. Journal of Biological Chemistry, 258: 4091-4097, 1983

• E115-5, E123-48, E283-52-These antibodies are produced by hybridomas derived from mice immunized with a human pancreatic carcinoma cell line.

  Reactivity: The antibodies are tumor specific (epithelial) and react with blood group B glycolipids. Quantitative binding studies document a differential reactivity among the antibodies for a type 1 or type 2 linkage of the B determinant. Antibodies E115-2 and E123-48 bind preferentially to type 2 chain B glycolipids, whereas antibody E283-52 bind to types 1 and 2.

  Reference(s): Hansson, GC, Karlsson, KA, Larson, G, McKibbin, JM, Blaszczyk, M, Herlyn, M, Steplewski, Z and Koprowski. 1983. Mouse monoclonal antibodies against human cancer cells lines with specificities for blood group antigens. Journal of Biological Chemistry, 258: 4091-4097, 1983

  Contact:

  Meryle J. Melnicoff, Ph.D.
  Director, Business Development
  The Wistar Institute
  Phone: (215) 898-0049
  melnicoff@wistar.org