Generation of cytotoxic effector cells against human melanoma

Stanley P.L. Leong, Yuan Ming Zhou, Michael E. Granberry, Ti Fen Wang, Thomas M. Grogan, Catherine Spier, Ruby White, Abhay Mehta, Augustine Y. Lin

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)397-409
Number of pages13
JournalCancer Immunology Immunotherapy
Volume40
Issue number6
DOIs
StatePublished - Nov 1 1995

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Keywords

  • Generation
  • Lymphocytes
  • Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Leong, S. P. L., Zhou, Y. M., Granberry, M. E., Wang, T. F., Grogan, T. M., Spier, C., White, R., Mehta, A., & Lin, A. Y. (1995). Generation of cytotoxic effector cells against human melanoma. Cancer Immunology Immunotherapy, 40(6), 397-409. https://doi.org/10.1007/BF01525391