Induced melanoma rejection.

Treatments which heighten the immune response can inhibit tumor growth in susceptible hosts. For example, BCG administered with tumor cells or injected into established intradermal tumors (1, 2) resulted in specific, systemic tumor immunity in guinea pigs. These procedures, however, depended upon direct contact of BCG and tumor cells; contralateral challenges were less effective (3). Another approach, effective with cutaneous neoplasms, involved the use of sensitizing agents such as dinitrochlorobenzene (DNCB) or purified protein derivative (PPD) of tuberculin (4). Such agents elicited delayed hypersensitivity reactions (cellular immunity) at sites of neoplastic lesions, followed by regression and reduced incidence of new lesions. This form of local sensitization therapy, however, requires prior identification of superficial neoplastic lesions, and might not generate systemic tumor immunity if applied some distance away from tumor cells. In mice, alloantigenic tumor cells stimulating a host rejection response have provided protection against other tumor cells to which the untreated hosts are susceptible (5, 6). In the latter study, alloantigenic (B16) melanoma implantation preceded by one week the contralateral challenge by Harding-Passey (H-P) melanoma to H-P-susceptible BALB/c mice, resulting in an induced systemic immunity against the H-P melanoma. But, not every H-P-challenged BALB/c recipient was adequately protected by the alloantigenic B16 melanoma pretreatment. Only 40% rejected their H-P implants, about 30% exhibited retarded H-P growth, and 30% indicated no anti-H-P protection when compared with untreated control hosts. We have, therefore, sought, and found, more effective protection in the form of strongly alloantigenic normal tissue implants, i.e., spleen and liver cells. Moreover, the use of more precisely genetically controlled antigenic variants found in various inbred mouse strains has led to results tending to rule out explanations of induced tumor rejection due to cross-reactions. Our findings are consistent with the possible adjuvant effect of alloantigenic tissue implants leading to augmentation of an otherwise inadequate tumor immunity. Finally, the results indicate that the induced tumor immunity is systematic and persistent.