Problems with the isolation of lymphoid clones with reactivity to human tumors

The development of monospecific lymphoid reagents directed against autologous human tumors is a primary goal of our laboratory. Our approach using fresh human tumors as both targets in cytotoxicity assays and stimulators in proliferative assays with other appropriate controls makes possible a careful analysis of the reactivities present following either direct expansion in Interleukin 2 (IL-2) or following mixed lymphocyte tumor interaction and subsequent limiting dilution cloning. In addition, the activity of cells stimulated by IL-2 and subsequently cloned with fresh tumor lytic capability is discussed. These lymphokine activated killer (LAK) clones lyse multiple fresh human tumors but not fresh normal cells. The use of these expanded reagents with appropriate specificities may be useful in the adoptive immunotherapy of human malignancy. Our initial results as well as some of the difficulties associated with this approach are presented.