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Generation of cytotoxic effector cells against human melanoma

  • Original Article
  • Generation, Lymphocytes, Melanoma
  • Published:
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Abstract

Metastatic or tumor-draining lymph nodes from six of nine melanoma patients undergoing lymph node dissection for metastatic melanoma generated cytotoxic T cells against autologous melanoma when these lymph node cells were treated by in vitro sensitization and recombinant interleukin-2 (IL-2). During the initial lymphocyte culture (2–6 weeks), cross-reactivity with autologous tumor cells, K562 and Daudi cells was usually noted. Cold-target inhibition assay with K562 and Daudi showed K562/Daudi-associated antigens on melanoma cells. During the later phase of lymphocyte culture with repeated in vitro sensitization (over 6–10 weeks), cytotoxicity was noted against autologous and allogeneic melanoma cells but not against K562, Daudi cells or autologous fibroblasts. Repeated in vitro sensitization resulted in the selection of specific cytotoxic lymphocytes against melanoma. Cold-target inhibition assay with autologous and allogeneic melanoma cells revealed shared and individual antigens. Using blocking monoclonal antibodies, MHC-restricted killing was noted in the autologous system. Further, both the autologous and allogeneic systems could be mediated through adhesion molecules such as ICAM-1 and LFA-3 on melanoma cells and LFA-1 on T cells. This study suggests that a constellation of cytotoxic effector cells and melanoma-associated antigens may be pivotal in tumor killing. Thus, future adoptive immunotherapy should modulate and enhance this complex interaction.

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Authors and Affiliations

  1. Department of Surgery, University of Arizona, 85724, Tucson, AZ, USA

    Stanley P. L. Leong, Yuan-Ming Zhou, Michael E. Granberry & Ti-Fen Wang

  2. Arizona Cancer Center, University of Arizona, 85724, Tucson, AZ, USA

    Stanley P. L. Leong, Yuan-Ming Zhou, Michael E. Granberry & Thomas M. Grogan

  3. Department of Pathology, University of Arizona, 85724, Tucson, AZ, USA

    Thomas M. Grogan & Catherine Spier

  4. Transfusion Medicine, College of Medicine, University of Arizona, 85724, Tucson, AZ, USA

    Ruby White

  5. T Cell Sciences Inc., 02139, Cambridge, MA, USA

    Abhay Mehta & Augustine Y. Lin

  6. Department of Surgery, University of California, San Francisco/Mount Zion Cancer Center, P.O. Box 7921, 94120, San Francisco, CA, USA

    Stanley P. L. Leong

Authors
  1. Stanley P. L. Leong
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  2. Yuan-Ming Zhou
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  3. Michael E. Granberry
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  4. Ti-Fen Wang
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  5. Thomas M. Grogan
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  6. Catherine Spier
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  7. Ruby White
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  8. Abhay Mehta
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  9. Augustine Y. Lin
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Additional information

This work was supported by an Elsa, U. Pardee Foundation grant, the Arizona Chronic Disease Research Commission grant and partly by grant CA23074 from the National Institutes of Health, Bethesda, MD, 20892

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Leong, S.P.L., Zhou, YM., Granberry, M.E. et al. Generation of cytotoxic effector cells against human melanoma. Cancer Immunol Immunother 40, 397–409 (1995). https://doi.org/10.1007/BF01525391

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  • DOI: https://doi.org/10.1007/BF01525391

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