PHASE-I CLINICAL-TRIAL WITH A HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX NONRESTRICTED CYTOTOXIC T-CELL LINE (TALL-104) IN DOGS WITH ADVANCED TUMORS

The human TALL-104 cell line is endowed with a uniquely potent MHC non restricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, thi s study was conducted to evaluate the possible toxicity and efficacy o f this new cell therapy in a superior animal model with spontaneous tu mors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study. All dogs had fai led all other available treatments and had very limited life expectanc y. Cyclosporin A was administered p.o. (10 mg/kg/day) starting from th e day before TALL-104 cell administration throughout the treatment to prevent rejection of the xenogeneic effecters. Lethally irradiated (40 Gy) TALL-104 cells (10(8)/kg) were administered systemically followin g two treatment schedules. In the first schedule, the cells were given every other day for 2 weeks in a row and then once a week for 3 addit ional weeks; in the second schedule, TALL-104 cells were administered daily for a total of 5 days. None of the 19 cases showed significant c linical or laboratory toxicity; in addition, none of the dogs had to b e withdrawn from the study because of immediate adverse reactions to t he infusions. The severe side effects usually associated with classica l lymphokine-activated killer therapy in association with high doses o f interleukin 2, such as ''capillary leak syndrome,'' were absent in t his study. Remarkably, TALL-104 therapy induced various degrees of ant itumor effects in 7 of the 19 dogs, including 1 complete response (con tinuing at +13 months), three partial responses (duration of 2 months, 3 months, and continuing at +2 months), and three transient responses . Clinical responses and immunological parameters correlated well in e ach case. Taken together, these data indicate that systemic administra tion of lethally irradiated TALL-104 cells in the absence of exogenous interleukin 2 may be regarded as a safe and promising adjuvant type o f treatment for advanced cancer patients.