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Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases.

Publication ,  Journal Article
Slingluff, CL; Darrow, T; Vervaert, C; Quinn-Allen, MA; Seigler, HF
Published in: J Natl Cancer Inst
September 7, 1988

Human T-cell populations specifically cytotoxic for autologous melanoma cells have been successfully generated from lymph node cells obtained from seven consecutive patients. The lymph node cells were stimulated in vitro with autologous irradiated melanoma cells; stimulation was repeated every 10-15 days at a tumor cell-to-lymphocyte ratio of approximately 1:20. Cytotoxic activity was assessed by a 4-hour 51Cr release assay. Mean lysis of autologous tumor cells was 47% at an effector-to-target cell ratio of 20:1, while mean lyses of the human myeloid leukemia cell line K562, allogeneic melanoma cells, and an osteosarcoma cell were 20%, 13%, and 11%, respectively. There was no lysis of autologous fibroblasts, fresh lymphocytes, or phytohemagglutinin-stimulated blasts. Three grades of specificity developed sequentially. In grade I, lysis of autologous tumor cells exceeded lysis of allogeneic tumor cells but did not exceed lysis of K562 cells. In grade II, lysis of autologous tumor cells exceeded lysis of K562 cells and all allogeneic tumor cells tested. In grade III, potent lysis of autologous tumor cells (greater than 40%) exceeded lysis of K562 cells and of all allogeneic tumor cells tested. All seven lymphocyte populations reached or exceeded grade I. Six reached or exceeded grade II. Two progressed to grade III. The generated cells were T cells, as determined by phenotypic analysis with flow cytometry. CD4+ cells and CD8+ cells accounted for 83%-100% of the cells. CD8+ T cells were separated from CD4+ T cells by panning with OKT8 and OKT4 antibodies. The resulting CD8-enriched and CD4-enriched populations were compared as effectors in cytotoxicity assays. The results suggest that the cell responsible for lysis of autologous tumor cells is CD8+. The methods used in this study have repeatedly resulted in the successful generation of cytotoxic T lymphocytes specifically cytotoxic for autologous melanoma cells; it is suggested that these cells have potential application for adoptive immunotherapy of melanoma.

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Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

September 7, 1988

Volume

80

Issue

13

Start / End Page

1016 / 1026

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Oncology & Carcinogenesis
  • Melanoma
  • Lymphocyte Activation
  • Lymph Nodes
  • Killer Cells, Natural
  • Immunotherapy
  • Humans
  • Cytotoxicity, Immunologic
  • Antigens, Surface
 

Citation

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Slingluff, C. L., Darrow, T., Vervaert, C., Quinn-Allen, M. A., & Seigler, H. F. (1988). Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases. J Natl Cancer Inst, 80(13), 1016–1026. https://doi.org/10.1093/jnci/80.13.1016
Slingluff, C. L., T. Darrow, C. Vervaert, M. A. Quinn-Allen, and H. F. Seigler. “Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases.J Natl Cancer Inst 80, no. 13 (September 7, 1988): 1016–26. https://doi.org/10.1093/jnci/80.13.1016.
Slingluff CL, Darrow T, Vervaert C, Quinn-Allen MA, Seigler HF. Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases. J Natl Cancer Inst. 1988 Sep 7;80(13):1016–26.
Slingluff, C. L., et al. “Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases.J Natl Cancer Inst, vol. 80, no. 13, Sept. 1988, pp. 1016–26. Pubmed, doi:10.1093/jnci/80.13.1016.
Slingluff CL, Darrow T, Vervaert C, Quinn-Allen MA, Seigler HF. Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases. J Natl Cancer Inst. 1988 Sep 7;80(13):1016–1026.
Journal cover image

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

September 7, 1988

Volume

80

Issue

13

Start / End Page

1016 / 1026

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Oncology & Carcinogenesis
  • Melanoma
  • Lymphocyte Activation
  • Lymph Nodes
  • Killer Cells, Natural
  • Immunotherapy
  • Humans
  • Cytotoxicity, Immunologic
  • Antigens, Surface