Effect of combined adoptive immunotherapy and radiotherapy on tumor growth

Advanced squamous cell carcinomas of the head and neck are difficult to con trol despite optimal surgery, radiotherapy and/or chemotherapy, and the tum ors are usually not immunogenic. Because of the anatomic accessibility of t he tumors, local adoptive immunotherapy of these tumors is feasable and may interact with radiotherapy to retard tumor growth. It is hypothesized that antigens released from tumor cells injured by radiation may stimulate, in the presence of interleukin-2, an enhanced immunocytodestruction of Live tu mor cells by adoptively transferred lymphokine activated killer cells and r ecruited tumor cytotoxic cells. DBA/2 mice were injected subcutaneously wit h 5 x 10(5) syngeneic squamous cell carcinoma cells in the thigh and the re sulting tumors were treated for two weeks with daily peritumoral injections of interleukin-2 (1,000 International Units) or saline, four radiation tre atments of 625 cGy each, and four peritumoral injections of 10(7) lymphokin e activated killer cells. The results suggested that radiotherapy combined with peritumoral injection of lymphokine activated killer cells and interle ukin-2 resulted in a significant reduction (P < 0.01) of tumor size whereas radiation alone, at the same dose, failed to produce a significant effect. Such results may have direct clinical application in enhancing the respons e of tumors to radiotherapy and in reducing the incidence of tumor recurren ce. (C) 1999 Wiley-Liss, Inc.