Prospects for T Cell Immunotherapy of Tumours by Vaccination with Immunodominant and Subdominant Peptides

  1. Derek J. Chadwick Organizer and
  2. Joan Marsh
  1. Cornelis J. M. Melief and
  2. W. Martin Kast

Published Online: 28 SEP 2007

DOI: 10.1002/9780470514672.ch7

Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers

Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers

How to Cite

Melief, C. J. M. and Kast, W. M. (2007) Prospects for T Cell Immunotherapy of Tumours by Vaccination with Immunodominant and Subdominant Peptides, in Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers (eds D. J. Chadwick and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470514672.ch7

Author Information

  1. Department of Immunohematology and Blood Bank, University Hospital Leiden, Building 1, E3-Q, PO Box 9600, 2300 RC Leiden, The Netherlands

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471950264

Online ISBN: 9780470514672

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Keywords:

  • T cell immunotherapy;
  • vaccination;
  • peptides;
  • autoantigens;
  • adoptive transfer

Summary

Immunotherapy of tumours by adoptive transfer of cytotoxic T lymphocytes (CTL) is now feasible in experimental murine systems. These CTL recognize peptide sequences of defined length presented by major histocompatibility complex (MHC) class 1 molecules. Effective eradication of large tumour masses requires co-administration of interleukin 2. Tumour escape strategies are numerous but in various instances can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic virally induced tumours and other tumours requires novel strategies to overcome T cell inertia. We propose a strategy in which CTL are raised against target molecules of choice including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The steps proposed include: (1) identification of target molecules of choice. (2) Identification in these target molecules of peptides fitting MHC allele-specific peptide motifs involved in peptide binding to MHC molecules. (3) Evaluation of actual binding of such peptides to specific MHC class I molecules. (4) In vitro CTL response induction by such peptides, presented by highly efficient antigen-presenting cells such as antigen processing-defective cells carrying empty MHC class I molecules loaded with a single peptide or dendritic cells. Both types of cells are capable of primary CTL response induction in vitro. (5) Evaluation of proper processing by the demonstration of tumour cell lysis by these CTL. (6) Adoptive transfer of tumour-specific CTL generated in vitro or vaccination with peptides. These various steps have now been taken for several viruses, virally induced tumours and other types of tumours and the first indications that this strategy is useful have been obtained.