A preclinical model to assess the antigenicity of an HLA-A2 melanoma cell vaccine

Cancer. 1993 Aug 1;72(3):750-9. doi: 10.1002/1097-0142(19930801)72:3<750::aid-cncr2820720319>3.0.co;2-v.

Abstract

Background: The authors have demonstrated that immunization with melanoma whole-cell vaccine (MCV) augments T-cell responses to melanoma and that cytotoxic T-cells (CTL) recognize allogeneic melanoma-bearing shared HLA-A antigens. A preclinical model was developed to assess CTL activation in vitro using melanoma lines as stimulators. HLA-A2 expression is predominant in melanoma patients and plays a role in HLA class I restricted CTL killing of melanomas. The authors hypothesized that a MCV consisting of allogeneic HLA-A2 melanomas may be as good as autologous melanoma MCV for HLA-A2 patients.

Methods: CTL were generated from peripheral blood lymphocytes of patients with HLA-A2 melanoma by stimulation with autologous melanoma, allogeneic melanoma (HLA-A2 or non-HLA-A2), or allogeneic MCV (mixed HLA-A2 and non-HLA-A2 melanomas).

Results: HLA-A2 MCV and autologous melanoma were similar and significantly better stimulators than the others. Specificity also was supported by CTL killing and mixed lymphocyte tumor reaction assays.

Conclusions: These studies provide important information for the studying immunization of patients with HLA-A2 melanoma with an allogeneic HLA-A2 MCV in a Phase I clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Cell Line
  • Cytotoxicity, Immunologic / immunology
  • HLA-A2 Antigen / immunology*
  • Humans
  • Immunotherapy
  • Lymphocyte Activation
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • Vaccines / immunology*

Substances

  • Antigens, Neoplasm
  • HLA-A2 Antigen
  • Vaccines