Susceptibility of human and murine drug-resistant tumor cells to the lytic activity of rIL2 - activated lymphocytes (LAK)

Abstract

This article surveys the available data on the sensitivity of drug-resistant tumor cells to recombinant interleukin 2 (rIL2)-activated lymphocytes (LAK). In our own study, three different experimental systems were used: in vitro treatment of tumor cells with an anticancer drug followed by the use of surviving cells as targets of LAK; use of pairs of drug-resistant and drug-sensitive cell sublines; analysis of several tumor clones obtained from the same tumor. The antitumor activity of LAK was evaluated both by the ⁵¹Cr release and the human tumor clonogenic assay (HTCA). In all the experimental systems used, drug-resistant tumor cells were found to be significantly lysed by LAK, with a consistent trend towards a higher susceptibility than their drug-sensitive counterparts. A positive correlation between the sensitivity to LAK and the ID₅₀ for doxorubicin (Dx) was found in 44 melanoma clones analyzed, suggesting that spontaneously drug-resistant clones have a higher sensitivity to LAK than the drug-sensitive clones. Drug-resistant cells were also more sensitive to antibody and complement-mediated lysis, whereas the higher lysis of drug-resistant tumor cells exerted by LAK was maintained in a lectin dependent cytotoxicity assay. These data offer a rationale for combining chemotherapy with adoptive immunotherapy in the treatment of cancer. Moreover, studying the reasons for the higher LAK sensitivity of drug-resistant tumor cells may provide insights into the mechanisms by which tumor cells can resist LAK action.