INDUCTION OF TUMOR-IMMUNITY BY INTACT IRRADIATED LEUKEMIC B-CELLS (BCL1) BEARING A TUMOR-ASSOCIATED CELL-SURFACE IDIOTYPE AND THE COSTIMULATORY B7 MOLECULE

The idioptypic (Id) determinant of immunoglobulin expressed on the cel l surface of malignant B cells represents a prototypical tumor-associa ted antigen (TAA), which has been used in a purified soluble form for active immunization in experimental tumor models and human hematologic al malignancies. Using a spontaneous transplantable murine model of B cell leukemia/lymphoma (BCL1), we have demonstrated the expression of the B7 costimulatory molecules in addition to the previously described Id determinant and class II major histocompatibility antigens. Intact irradiated BCL1 cells bearing these distinct determinants induced lon g lasting antitumor immunity in naive syngeneic mice. Induction was do se-dependent and most effective when three doses of 30 x 10(6) intact irradiated BCL1 cells were given at intervals of 7-10 days. The induce d immunity protected 96% of 28 mice inoculated with a lethal dose of 1 0(5)-10(6) nonirradiated BCL1 cells and 85% of 27 mice given a second challenge, whereas control mice died on day 20 after inoculation with 10(6) BCL1 cells. Adoptive transfer of splenocytes derived from immune mice did not induce leukemia in syngeneic recipients. Such splenocyte s, harvested more than 365 days following immunization and administere d together with fresh BCL1 cells to adoptive recipients, were able to confer protection for 90 days, even following a second challenge given 104 days after the first one. BCL1 immune splenocytes transferred int o BCL1-bearing mice exerted a therapeutic effect, preventing leukemia onset for at least 180 days. Our results demonstrate the ability of tu mor cells to trigger effective anti-tumor immunity. These findings cou ld ultimately be applied to the prevention of tumor relapse in treatme nt of hematological and other malignancies expressing sing TAA, class II MHC antigen and costimulatory molecules.