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Antitumor Effects of Interleukin 2 Liposomes and Anti-CD3-Stimulated T-Cells against Murine MCA-38 Hepatic Metastasis¹

Departments of Surgery [C. M. L., A. S. L.], and Pediatrics [J. L. P., P. M. A., E. K.], University of Minnesota, Minneapolis, Minnesota 55455; Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 [J. B. O.]; Immunotherapy Laboratory, Program Resources, Inc. [C. M. L., W. J. U., A. C. O.], and Biological Response Modifiers Program [D. L. L.], National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

The stimulation of murine splenocytes with the monoclonal antibody anti-CD3 and interleukin 2 (IL-2) results in the propagation of large numbers of cells (T-activated killer, T-AK) which demonstrate high therapeutic efficacy when infused with IL-2 into mice bearing pulmonary metastases. Interleukin 2 infusions are required to maintain the function of the adoptively transferred cells. Recent data demonstrate that the therapeutic efficacy can be enhanced by encapsulating IL-2 in liposomes. The present work tested the combination of T-AK cells with IL-2 liposomes in an immunotherapy model utilizing the MCA-38 murine colon adenocarcinoma.

Expansion of murine splenocytes was achieved with anti-CD3 monoclonal antibody plus IL-2 and was consistently greater than 50-fold during a 9-day culture period. Cytolytic activity of the murine T-AK cells was mediated primarily by Lyt-2⁺ cells. In vivo results demonstrate synergistic therapeutic efficacy of the combination of IL-2 liposomes and T-AK cells. Evaluation of the in vivo distribution of these T-AK cells utilizing congenic mice demonstrates that Lyt-2⁺ cells from these in vitro cultures infiltrate hepatic metastases in vivo. The activation of lymphocytes with anti-CD3 monoclonal antibody and IL-2 appears to be a reproducible and convenient method of producing cells capable of producing antitumor effects in models of adoptive immunotherapy.

¹ This work was supported in part by NIH Grants CA 47097 and AM 13083, Program Resources Inc., and Oncotherapeutics Inc. This research was also sponsored, at least in part, by the National Cancer Institute, Department of Health and Human Services, under Contract N01-CO-74102 with Program Resources, Incorporated/DynCorp. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. C. M. L. is a recipient of the American College of Surgeons Scholarship 1990. P. M. A. is supported in part by the American Cancer Society Clinical Oncology Career Development Award 90-163. E. K. is a fellow of the Medical Research Council of Canada. J. L. P. is an established investigator of the American Heart Association and is supported in part by NIH Grant DK13083. J. B. O. is supported in part by NIH Minority Research Enhancement Program Grant GM3 7753-04.

² To whom requests for reprints should be addressed, at the National Cancer Institute/P.O. Box b, Frederick Cancer Research and Development Center, Program Resources, Inc., Dyncorp, Frederick, MD 21702.

Received 10/25/90. Accepted 2/ 5/91.

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