Adoptive chemoimmunotherapy (ACIT) using recombinant interleukin 2 (rIL2)-stimulated effector cells in conjunction with the chemotherapeutic drugs doxorubicin hydrochloride (DOX) was successful in curing 70% of mice bearing Stage I murine renal cancer (Renca). Conversely, chemotherapy or adoptive immunotherapy (ACIT) alone was unable to render mice disease free. Similarly, simultaneous intravenous and intraperitoneal administration of ACIT to mice bearing advanced (Stages II or III) Renca was able to render 80% of these mice disease free, while administration of ACIT by either route alone was unsuccessful. These observations demonstrate that the antitumor effects of AIT are increased when used in conjunction with chemotherapeutic drugs and emphasize the need to efficiently deliver the ACIT to all sites of tumor growth. Further studies have demonstrated that both activated natural killer (NK) cells and lymphokine activated killer (LAK) cells which can function in ACIT are generated from the asialo GM1+, Lyt2-, L3T4 lymphocyte subset and suggest that LAK cells arise largely by differentiation or activation of NK cells. Additional studies are designed to determine the mechanism(s) by which BRMs induce augmented NK activity and an accumulation of NKactive large granular lymphocytes (LGL) in the liver. The results have demonstrated that a single administration of these BRMs augments NK activity in the liver, that repeated administration of these BRMs induces a further increase in both NK activity and LGL number, and that LGL contribute to BRM-induced inflammation in the liver. These observations are currently being used to determine the contribution of NK cells to BRM-induced antimetastatic effects in nonlymphoid organs, which are often sites of metastasis formation during the progression of human cancer.
