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Lysis by Activated Lymphocytes of Melanoma and Small Cell Lung Cancer Cells Surviving in Vitro Treatment with Mafosfamide¹

Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan [C. G-P., M. R., G. F., G. P.], and Istituto di ricerche farmacologiche Mario Negri, Milan [E. E.], Italy

Six short term-cultured melanoma cell lines and one small cell lung cancer cell line were treated in vitro with the alkylating agent mafosfamide. The sensitivity of the surviving cells to in vitro lysis by recombinant interleukin 2-activated autologous and allogeneic lymphocytes was then investigated. In no case did chemo-surviving tumor cells appear less sensitive to lymphocyte-mediated lysis than untreated counterparts. In three of seven cases (two of which were derived from the same patient), chemo-selected cells were even more sensitive to cytotoxic lymphocytes, a difference not explained by a different distribution of neoplastic cells in the various cell cycle phases. We also studied the inhibitory activity of activated lymphocytes on the clonogenic potential of chemo-surviving tumor cells by the human tumor clonogenic assay. Inhibitions of tumor cell growth in the two patients tested were 100 and 94%, respectively; the activity of lymphocytes was dependent on the coculture time and the effector/target cell ratio. These data indicate that in vitro treatment with mafosfamide does not select cells resistant to the action of activated lymphocytes and that, given the right experimental conditions, these immune effectors can completely lyse tumor cells.

¹ This work was partially supported by "Associazione italiana per la ricerca contro il Cancro" of Milan, Italy.

² To whom requests for reprints should be addressed.

Received 10/13/86. Revised 1/ 5/87. Accepted 2/16/87.