Antitumor and antimetastatic properties of an anti-idiotypic monoclonal antibody in relation to N-glycolyl-containing gangliosides

A.M. VAZQUEZ; MARIANO R. GABRI; A.M. HERNÁNDEZ; D.F. ALONSO; I. BEAUSOLEIL; D.E. GOMEZ; R. PEREZ

San Francisco, CA.

Congreso; 91st. Annual Meeting, American Association for Cancer Research (AACR); 2000

American Association for Cancer Research (AACR)

Gangliosides are acidic glycolipids expressed in many normal tissues, but they are overexpressed in several solid tumors, including breast cancer and melanoma. A strategy for inducing an effective immune response against gangliosides is the use of anti-idiotypic antibodies as antigen specific immunomodulators. We examined the antitumor effects of 1E10 monoclonal antibody, an anti-idiotypic IgG to an IgM monoclonal antibody, named P3, that reacts specifically with N-glycolyl-containing gangliosides. Two murine tumor cell lines positive for the P3 antibody, F3II mammary carcinoma (BALB/c) and B16 melanoma (C57BL/6), were employed. In BALB/c mice, administration of 4 i.p. doses at 14-day intervals of 50 mg of 1E10 coupled to keyhole limpet hemocyanin (KLH) with Freund’s adjuvant induced a strong IgG Ab3 response. Immunization with 1E10-KLH significantly reduced s.c. tumor growth of F3II carcinoma cells and the number of spontaneous lung metastases. Furthermore, the effect of 1E10 on lung metastases was evaluated in C57BL/6 mice injected i.v. with B16 melanoma cells. Interestingly, i.v. administration of 10 mg of uncoupled 1E10 antibody 10 to 14 days after inoculation of B16 cells dramaticaly reduced the number of experimental metastases in comparision with lungs from mice treated with an irrelevant IgG. The present data suggest that 1E10 monoclonal antibody may activate a strong antitumor response against melanoma and mammary tumor cells. Supported by ELEA Laboratory (Buenos Aires, Argentina).