Systemic adoptive transfer of immunity and low-dose irradiation eradicate metastases of 13762A rat mammary adenocarcinoma

Abstract

Rats cured of poorly immunogenic 13762A tumor by a combination of surgery and cyclophosphamide (CY) treatments produced peritoneal exudate cells (PEC) that prevented tumor growth when transferred to naive recipients, but they were ineffective against established tumor. A highly immunogenic 13762A clone (18A) induced PEC lymphocytes that completely reversed the growth of established primary tumor and of lymph-node metastases. 18A-immune PEC alone strongly inhibited tumors of 7 days' duration, but only moderately suppressed 14-day tumors, and had no effect on 21-day tumors. Irradiation (450 R) of rats prior to tumor transplantation improved the effectiveness of the PEC given at 7 days, but the benefit had gone by 14 days. Long-term T-cell depletion prior to tumor challenge allowed PEC inhibition of 7- and 14-day tumors, but not 21-day tumors. The most potent strategy was the administration of 450 R followed immediately by immune PEC. When rats with 21-day tumors were so treated, the metastases grew temporarily to a maximum diameter of 2-5 cm and then completely regressed. We concluded that a combination of immune T cells and 450 R can cure established, massive metastases, probably through a combination of an increase in the numbers of T-cell effectors and elimination of suppressor cells.