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Adoptive Cellular Immunotherapy of Human Ovarian Carcinoma Xenografts in Nude Mice

Natural Immunity and Clinical Investigations Sections, Biological Therapeutic Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, NIH, Frederick Cancer Research Facility, Frederick, Maryland 21701 [J. R. O., H. R. P., P. M., H. C. S.], and Experimental Therapeutics Section, Medicine Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205 [R. F. O., T. C. H.]

Adoptive cell therapy with various purified populations of human lymphoid and monocytoid effector cells which have been in vitro activated with recombinant interleukin 2 and -interferon was performed in an in vivo nude mouse model of human ovarian cancer. Administration i.p. of human interleukin 2-activated populations of large granular lymphocytes resulted in a significant extension of mean survival time (30 to 60 days) in this ovarian carcinoma model. In addition, T-cells activated with interleukin 2, in a similar fashion to large granular lymphocytes, also significantly prolonged survival of animals with ovarian carcinoma. In contrast, monocytes, with or without -interferon activation, did not improve survival of tumor-bearing mice. In vitro results using direct isotopic release assays to measure efficacy of effectors against the ovarian cancer cells before and after activation, especially the activated natural killer cells, paralleled the effects on survival in the nude mouse model. However, the results with T-cells were somewhat inconsistent in vitro regarding their in vivo efficacy. We assume this is due to a delayed generation of activated killing in T-cells that is generated in vivo. These experimental results in this model system of human ovarian cancer indicate that transfer of autologous activated cells may have a role in the treatment of ovarian cancer patients.

Received 2/ 4/86. Revised 5/ 7/86. Accepted 5/16/86.

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