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Induction of lymphokine-activated killer cytotoxicity with interleukin-2 and tumor necrosis factor-α against primary lung cancer targets

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Summary

Human peripheral blood mononuclear cells (PBM) activated with recombinant interleukin-2 (IL-2) generate potent lytic activity (LAK) against a variety of malignant cells. IL-2 alone is sufficient for LAK generation, but high concentrations are needed to generate optimal cytotoxicity. Our recent studies based on combinations of biological agents indicated that alternative activation pathways may exist. Synergy for LAK induction was investigated using IL-2 and tumor necrosis factor-α (TNF). Single-cell suspensions of primary human lung carcinomas were prepared from seven established cell lines and 32 fresh tumor specimens. Not only were all cell lines sensitive to allogeneic LAK, but also all fresh tumors were sensitive to some degree to both autologous and allogeneic LAK lysis measured by a 4-h 51Cr-release assay. LAK-mediated cytotoxicity, induced with a combination of human recombinant IL-2 (Cetus, 100 U/ml) and TNF (Genentech, 500 U/ml), showed a mean fourfold increase (range 0.7–16.3) over IL-2 alone. No lytic activity was generated from PBM incubated with media or TNF alone. The sequence dependence of adding IL-2 and TNF in enhancing cytolytic activity was also studied. In vitro kinetics data revealed that the addition of TNF 2–6 h before the addition of IL-2 greatly increased LAK activity over that obtained from the simultaneous addition of the two cytokines. These results demonstrated (a) the synergy of IL-2 and TNF for generating LAK; (b) the lysis of fresh primary lung cancer cells by LAK; and (c) the sequence dependence of IL-2 and TNF for the induction of optimal LAK activity.

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Authors and Affiliations

  1. Department of Thoracic Surgery, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 109, 77030, Houston, TX, USA

    Stephen C. Yang & Jack A. Roth

  2. Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, 77030, Houston, Texas, USA

    Laurie Owen-Schaub, Elizabeth A. Grimm & Jack A. Roth

  3. Department of General Surgery, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, 77030, Houston, Texas, USA

    Elizabeth A. Grimm

  4. Department of General Surgery, University of Texas Health Science Center at Houston, 6431 Fannin Street, 77030, Houston, Texas, USA

    Stephen C. Yang

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  1. Stephen C. Yang
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  2. Laurie Owen-Schaub
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  3. Elizabeth A. Grimm
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  4. Jack A. Roth
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This work was supported by NCI Grants RO2-CA45225 and CAO 9611-01, and by an award from the Prouss Foundation

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Yang, S.C., Owen-Schaub, L., Grimm, E.A. et al. Induction of lymphokine-activated killer cytotoxicity with interleukin-2 and tumor necrosis factor-α against primary lung cancer targets. Cancer Immunol Immunother 29, 193–198 (1989). https://doi.org/10.1007/BF00199995

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  • DOI: https://doi.org/10.1007/BF00199995

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