TALL-104 cell therapy of human solid tumors implanted in immunodeficient (SCID) mice.
We have developed a novel approach to adoptive therapy of cancer based on the use of a human T cell line (TALL-104) which is endowed with major histocompatibility complex non-restricted cytotoxic activity against a broad range of tumors and across several species, while sparing cells from normal tissues. The present study investigates the efficacy of TALL-104 cell therapy in severe combined immunodeficient (SCID) mice implanted with human solid tumors. The human cell lines DU-145 (prostate cancer), A549 (lung carcinoma) and WM451 (melanoma) were implanted subcutaneously (s.c.) in the flank region of the mice. Multiple intraperitoneal (i.p.) transfers of lethally irradiated TALL-104 cells into animals bearing small tumor masses (150 mg) resulted in 50-75% reduction of local tumor growth and complete prevention of pulmonary metastasis. In mice implanted s.c. with A549 cells, dramatic antitumor effects against both local and metastatic disease were observed when cell therapy was initiated after surgical excision of the primary tumor mass. In another set of experiments, the DU-145 and WM451 cells were injected intravenously (i.v.); cells disseminated aggressively in various organs and all animals died within 6-10 weeks from engraftment. However, experimental mice that received TALL-104 cell therapy i.p. daily, starting 1 week after tumor inoculation, showed longer survival and a slower tumor growth (as measured monthly by plasmatic levels of the sICAM-1 tumor marker). At necropsy 1/6 of these animals were disease free. Taken together, these data indicate the effectiveness of this novel antitumor agent in prolonging disease-free survival and controlling tumor growth and invasion.
Cesano
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Wistar Institute, Philadelphia, PA 19104, USA.
Visonneau
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S
Santoli
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D019264:Adoptive Transfer; D000818:Animals; D005720:Gamma Rays; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014183:Transplantation, Heterologous