This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cesano, A. Articles by Santoli, D. Search for Related Content PubMed PubMed Citation Articles by Cesano, A. Articles by Santoli, D.

Phase I Clinical Trial with a Human Major Histocompatibility Complex Nonrestricted Cytotoxic T-Cell Line (TALL-104) in Dogs with Advanced Tumors¹

The Wistar Institute, Philadelphia, Pennsylvania 19104 [A. C., S. V., J. O., D. S.], and Veterinary Oncology Services and Research Center, West Chester, Pennsylvania 19380 [K. A. J., K. W., K. C., L. R.]

The human TALL-104 cell line is endowed with a uniquely potent MHC nonrestricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, this study was conducted to evaluate the possible toxicity and efficacy of this new cell therapy in a superior animal model with spontaneous tumors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study. All dogs had failed all other available treatments and had very limited life expectancy. Cyclosporin A was administered p.o. (10 mg/kg/day) starting from the day before TALL-104 cell administration throughout the treatment to prevent rejection of the xenogeneic effectors. Lethally irradiated (40 Gy) TALL-104 cells (10⁸/kg) were administered systemically following 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 additional weeks; in the second schedule, TALL-104 cells were administered daily for a total of 5 days. None of the 19 cases showed significant clinical or laboratory toxicity; in addition, none of the dogs had to be withdrawn from the study because of immediate adverse reactions to the infusions. The severe side effects usually associated with classical lymphokine-activated killer therapy in association with high doses of interleukin 2, such as "capillary leak syndrome," were absent in this study. Remarkably, TALL-104 therapy induced various degrees of antitumor effects in 7 of the 19 dogs, including 1 complete response (continuing 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 each case. Taken together, these data indicate that systemic administration of lethally irradiated TALL-104 cells in the absence of exogenous interleukin 2 may be regarded as a safe and promising adjuvant type of treatment for advanced cancer patients.

¹ This work was supported in part by American Cancer Society Grant RD-391, the Connelly Foundation, the Parker Hughes Trust, and funds from Dr. Jeanne Rubenstone.

² To whom requests for reprints should be addressed, at The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104.

Received 2/15/96. Accepted 4/30/96.

This article has been cited by other articles:

				C. Brando, S. Mukhopadhyay, E. Kovacs, R. Medina, P. Patel, T. L. Catina, K. S. Campbell, and D. Santoli Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104 J. Leukoc. Biol., August 1, 2005; 78(2): 359 - 371. [Abstract] [Full Text] [PDF]

				G. G. Gomez, S. B. Read, L. E. Gerschenson, D. Santoli, A. Zweifach, and C. A. Kruse Interactions of the allogeneic effector leukemic T cell line, TALL-104, with human malignant brain tumors Neuro-oncol, April 1, 2004; 6(2): 83 - 95. [Abstract] [PDF]

				C. A. Kruse, S. Visonneau, B. K. Kleinschmidt-DeMasters, C. J. Gup, G. G. Gomez, D. B. Paul, and D. Santoli The Human Leukemic T-Cell Line, TALL-104, Is Cytotoxic to Human Malignant Brain Tumors and Traffics through Brain Tissue: Implications for Local Adoptive Immunotherapy Cancer Res., October 1, 2000; 60(20): 5731 - 5739. [Abstract] [Full Text]

				S. Visonneau, A. Cesano, D. L. Porter, S. L. Luger, L. Schuchter, M. Kamoun, M. H. Torosian, K. Duffy, C. Sickles, E. A. Stadtmauer, et al. Phase I Trial of TALL-104 Cells in Patients with Refractory Metastatic Breast Cancer Clin. Cancer Res., May 1, 2000; 6(5): 1744 - 1754. [Abstract] [Full Text] [PDF]

				B. Geoerger, C.-B. Tang, A. Cesano, S. Visonneau, S. Marwaha, K. D. Judy, L. N. Sutton, D. Santoli, and P. C. Phillips Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts Neuro-oncol, April 1, 2000; 2(2): 103 - 113. [Abstract] [PDF]

				S. Visonneau, A. Cesano, K. A. Jeglum, and D. Santoli Adjuvant Treatment of Canine Osteosarcoma with the Human Cytotoxic T-Cell Line TALL-104 Clin. Cancer Res., July 1, 1999; 5(7): 1868 - 1875. [Abstract] [Full Text] [PDF]

				D. L. Porter, J. M. Connors, V. M.D. Van Deerlin, K. M. Duffy, C. McGarigle, S. L. Saidman, D. G.B. Leonard, and J. H. Antin Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies J. Clin. Oncol., April 1, 1999; 17(4): 1234 - 1234. [Abstract] [Full Text] [PDF]

				T. Guillaume, D. B. Rubinstein, and M. Symann Immune Reconstitution and Immunotherapy After Autologous Hematopoietic Stem Cell Transplantation Blood, September 1, 1998; 92(5): 1471 - 1490. [Full Text] [PDF]

				A. Cesano, S. Visonneau, S. Deaglio, F. Malavasi, and D. Santoli Role of CD38 and Its Ligand in the Regulation of MHC-Nonrestricted Cytotoxic T Cells J. Immunol., February 1, 1998; 160(3): 1106 - 1115. [Abstract] [Full Text] [PDF]