SUCCESSFUL TREATMENT OF CANINE MALIGNANT HISTIOCYTOSIS WITH THE HUMANMAJOR HISTOCOMPATIBILITY COMPLEX NONRESTRICTED CYTOTOXIC T-CELL LINE TALL-104

The human MHC nonrestricted cytotoxic T-cell line TALL-104 exerts pote nt antitumor effects in animal models with both induced and spontaneou s cancers. The present report documents the ability of systemically de livered TALL-104 cells to induce durable clinical remissions in four o f four dogs with malignant histiocytosis (MH), The animals received mu ltiple i.v. injections of lethally irradiated (40 Gy) TALL-104 cells a t a dose of 10(8) cells/kg, ,,with (two dogs) or without (two dogs) cy closporin A, followed by monthly boosts. No significant clinical or la boratory toxicities developed during cell therapy; interestingly, a st rong correlation was found between the dogs' clinical and immunologica l responses, One dog with advanced disease (intrathoracic involvement) refractory to chemotherapy achieved a complete remission (CR) within 2 months of the first TALL-104 cell infusion, This dog died 14 months later of unrelated causes: histological analysis of its organs postmor tem revealed no evidence of neoplasia, thus confirming the achievement of CR also at the pathological level, The other three dogs with MH th at at diagnosis had multiple s.c. and cutaneous lesions and lymphadeno pathy, but no visceral involvement, were treated with TALL-104 cells a s single agent (no chemotherapy was administered), Two of these dogs a chieved a CR soon after cell therapy, and the third dog had two long-l asting partial responses; CR in this dog was later achieved by combine d administration of chemotherapy and cell therapy, None of the three d ogs that received cell therapy at diagnosis developed visceral disease in the similar to 9-22 months of follow-up. The clinical responses ex perienced by all four MH cases to TALL-104 cell therapy suggest the hi gh responsiveness of this canine tumor to these xenogeneic effecters a nd their therapeutic potential even in the most aggressive forms of th e disease.