Superior tumor protection induced by a cellular vaccine carrying a tumor-specific T helper epitope by genetic exchange of the class II-associated invariant chain peptide

Cancer Res. 2000 Nov 15;60(22):6427-33.

Abstract

Efficient loading of MHC class II molecules with a T helper epitope of choice can be achieved through genetic exchange of the MHC class II-associated invariant chain peptide (CLIP) sequence with a sequence encoding the helper peptide. We have now used this method to engineer a cellular vaccine that continuously expresses a tumor-specific helper epitope in a defined costimulatory context. We provide evidence (a) that this cellular vaccine induces peptide-specific helper T cells in vivo that are functional in protecting mice from challenge with a highly aggressive tumor, (b) that this vaccine can directly prime tumor-specific helper T cells in vivo, and (c) that this cellular vaccine is superior compared with similar cells loaded with synthetic T helper peptide in inducing tumor protection. In conclusion, cellular vaccines for activation of antigen-specific helper T cells can be greatly improved by the introduction of invariant chain constructs containing a T helper epitope by class II-associated invariant chain peptide exchange.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / physiology
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Lymphocyte Activation / immunology
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Retroviridae Proteins, Oncogenic / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transfection
  • Vaccination
  • Viral Envelope Proteins / immunology

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Retroviridae Proteins, Oncogenic
  • Viral Envelope Proteins
  • invariant chain