Successful treatment of canine malignant histiocytosis with the human major histocompatibility complex nonrestricted cytotoxic T-cell line TALL-104.
The human MHC nonrestricted cytotoxic T-cell line TALL-104 exerts potent antitumor effects in animal models with both induced and spontaneous cancers. The present report documents the ability of systemically delivered TALL-104 cells to induce durable clinical remissions in four of four dogs with malignant histiocytosis (MH). The animals received multiple i.v. injections of lethally irradiated (40 Gy) TALL-104 cells at a dose of 10(8) cells/kg, with (two dogs) or without (two dogs) cyclosporin A, followed by monthly boosts. No significant clinical or laboratory toxicities developed during cell therapy; interestingly, a strong correlation was found between the dogs' clinical and immunological 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 postmortem revealed no evidence of neoplasia, thus confirming the achievement of CR also at the pathological level. The other three dogs with MH that at diagnosis had multiple s.c. and cutaneous lesions and lymphadenopathy, but no visceral involvement, were treated with TALL-104 cells as single agent (no chemotherapy was administered). Two of these dogs achieved a CR soon after cell therapy, and the third dog had two long-lasting partial responses; CR in this dog was later achieved by combined administration of chemotherapy and cell therapy. None of the three dogs that received cell therapy at diagnosis developed visceral disease in the approximately 9-22 months of follow-up. The clinical responses experienced by all four MH cases to TALL-104 cell therapy suggest the high responsiveness of this canine tumor to these xenogeneic effectors and their therapeutic potential even in the most aggressive forms of the disease.
Visonneau
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The Wistar Institute, Philadelphia, Pennsylvania 19104, and Veterinary Oncology Services and Research Center, West Chester, Pennsylvania 19382, USA.
Cesano
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Tran
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Jeglum
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Santoli
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D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004283:Dog Diseases / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D054747:Histiocytic Sarcoma / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D009360:Neoplastic Cells, Circulating; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000528:radiation effects / Q000637:transplantation*
D016572:Cyclosporine