Development of Specific Cell-dependent Antibody During Growth of a Syngeneic Rat Sarcoma

A micro-cytotoxicity assay was adapted for the detection of cell-dependent antibodies (CDA). Using normal rat spleens as the source of effector cells such CDA activity was readily demonstrable in allo-immune sera tested on cultured sarcoma cells. The same technique was then used to examine for tumour specific antibodies in the sera of Hooded rats bearing a “non-immunogenic” syngeneic metastasizing sarcoma. During the early stages of tumour growth, at Days 7 and 14, tumour specific CDA cytotoxicity was detectable at high titres. By Day 21, however, this activity had completely disappeared from the serum. This cell-dependent cytotoxicity was tumour specific in that it did not kill cells from an unrelated syngeneic sarcoma, and the activity was probably confined to immunoglobulin G as detected by molecular weight separation techniques. Following tumour amputation at Day 21, this type of specific antibody activity rapidly re-appeared in the serum. The presence of tumour specific CDA showed an inverse correlation with the presence of specific inhibitors of cell-mediated immunity in the same sera. At no stage in tumour growth could complement-dependent cytotoxicity be detected in tumour bearing rat sera. It is concluded that cell-dependent cytotoxic activity is not associated with conventional complement dependence, that this CDA type of assay is exquisitely sensitive and is suitable for the detection of anti-TSTA antibodies in tumour bearing rats. The possible significance of CDA activity in syngeneic tumour immunity is discussed briefly. The results suggest that the role of humoral immune mechanisms in host resistance to tumour growth needs re-appraisal.