Human NK Resistant Tumor Cell Lysis is Effected by IL-2 Activated Killer Cells
In experimental animal systems, trarlsfer of cell populations immune to solid tumors has been successful in mediating the regression of such tumors. In human systems, much conflicting and confusing data has been reported attempting to define the analogous effector cells. Our approach to define human anti-tumor effectors cells was to avoid as many in vitro induced artifacts as possible, and to employ fresh (or cyropreserved, uncultured) surgical biopsy specimens of tumors as target cells, and to generate effectors in human serum with naturally occurring immune stimulants. We have found that normal or cancer patients1 PBL incubated for 2–3 days in preparations of IL-2, including purified recombinant IL-2 (RIL-2) acquires the unique capacity to kill human tumors in 4 hour chromium release assays (1–6). These lymphokine-activated killer cells (LAK) kill NK resistant fresh tumors with an efficiency and polyspecificity that has not been found reproducible in any other anti-tumor lytic system, and therefore provides yet another interesting and potentially biologically relevant system in which to examine the mechanism of cell mediated cytotoxicity. This report addresses some of the basic aspects of LAK killing, such as the killing efficiency of whole populations versus clones, kinetics of lysis as measured by the chromium release assay, correlation of chromium release with the expression of LAK effector cell markers, and morphology and phenotype of LAK effector cells, thereby setting the groundwork for further detailed studies of the mechanism of tumor killing by LAK.
KeywordsChromium Release Allogeneic Tumor Chromium Release Assay Surgical Biopsy Specimen Effector Target Ratio
Unable to display preview. Download preview PDF.
- 2.Grimm, E.A., Gorelik, E., Rosenstein, M.M., and Rosenberg, S.A. The lymphokine-activated killer cell phenomenon: In vitro and in vivo studies. Interluekins, Lymphokines, and Cytokines. S. Cohen and J. Oppenheim,(eds.). Academic Press, New York, pp. 739–746 (1983).Google Scholar
- 5.Rosenberg, S.A., Grimm, E.A., McGrogan, N., Doyle, M., Kawasaki, E., Koths, K., and Mark, D.F. Biologic activity of recombinant human interleukine-2 produced in E. Coli. Science. 223:1412–1415 (1984).Google Scholar
- 6.Grimm, E.A., and Rosenberg, S.A. The human lymphokine- activated killer cell phenomenon in Lymphokines. 9: Edgar Pick, (ed.) Academic Press, (in press).Google Scholar
- 8.Henney, C.S. Dintinction between NK cells and CTL in Advances in Exp. Med. Biol. 146:353–356 (1982).Google Scholar
- 10.Rayner, A.A., Grimm, E.A., Lotze, M.T., and Rosenberg, S.A. Demonstration of shared recognition and lysis of autologous and allogeneic fresh human tumors by cloned lymphokine-activated killer calls (LAK): Implications for immunotherapy. Surgical Forum (in press).Google Scholar
- 11.Rayner, A.A., Grimm, E.A., Lotze, M.T., Chu, E., and Rosenberg, S.A. Lymphokine-activated killer cells (LAK). Analysis of factors relevant to the immunotherapy of cancer. (submitted).Google Scholar
- 12.Rayner, A.A., Grimm, E.A., Wilson, D.J., and Rosenberg, S.A. Clonal and lytic analysis of IL-2 activated lymphocyte: Lymphokine-activated killer (LAK) cell clones lyse multiple fresh human targets, (submitted).Google Scholar
- 15.Kaufmann, Y. Lyt 2 negative and T cell growth factor independent cytotoxic T lymphocyte hybridomas. Adv. in Exp. Med. Biol. W.R. Clark and P. Goldstein (eds.) 146 (1982).Google Scholar
- 17.Mule, J.J., Shut, S., Schwarz, S., and Rosenberg, S.A. Successful adoptive immunotherapy of established pulmonary metastases of multiple sarcomas with lymphokine-activated killer cells and recombinant IL-2. Science, (in press).Google Scholar