The effect of alloimmunization on recurrence in an experimental colon cancer model

Primary bowel tumors were induced in Wistar/Furth (W/Fu) rats by 16 weekly injections of 1,2-dimethylhydrazine (DMH). After curative resection, 70% to 75% of control rats who receive no further treatment developed local or regional recurrence within 22 weeks. Rats immunized with three weekly subcutaneous inoculations of 1 X 10(6) irradiated (10,000 rad) Brown Norwegian (BN) X W/Fu F1 or Buffalo (Bu) tumor cells (both containing colon cancer tissue-type specific antigens [TSA] but differing from the W/Fu at Ag-B [histocompatibility] loci) developed recurrent tumor at a rate not significantly different from untreated or concurrent Ag-B antigen matched non-TSA treated controls. By 22 weeks after tumor resection, 63% of rats immunized with BN X W/Fu F1 colon adenocarcinoma and 52% of those immunized with Bu adenocarcinoma had recurred. Sixty-one percent and 44% were the respective recurrence rates for rats immunized with strain matched renal cell tissue. These data show nonspecific protection against tumor recurrence because of alloimmunization but clearly demonstrate the subordination of any beneficial colon cancer TSA immunotherapeutic effect by contained histocompatibility antigens. The problem of such nonspecific immune stimulation by alloantigen overriding an expected specific effect by TSA and possible alternative methods of immunization to prevent this phenomenon are discussed.