Tumor regression in tumor-bearing mice by inoculations of immunogenic somatic hybrid cells in combination with cyclophosphamide.

Some somatic hybrid cells prepared by cell fusion of MC-induced primary tumor cells with 8-azaguanine resistant L cells were immunogenic in the induction of specific resistance in syngeneic normal mice to the challenge of parental tumor cells. However, inoculations of immunogenic hybrid cells in tumor-bearing hosts evoked enhancement of tumor growth. In these mice with enhanced tumors, the level of immune complexes and antitumor antibodies in sera was more markedly elevated than in sera of untreated tumor-bearers, despite generation of effective cytotoxic T cells in the spleen. Enhancement was not observed by pretreatment with cyclophosphamide (CY), followed by treatment with hybrid cells, but tumor regression occurred. Complete tumor regression was observed in about 70% of animals treated with CY (100 mg/kg) plus viable hybrid cells (10(6)) three times at weekly intervals starting 1 week after tumor transplantation. Coincidental decreases of immune complexes and antitumor antibodies in sera were observed. The results suggest that suppression of the immunological escape mechanism is of primary importance in active tumor-specific immunotherapy.