Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia

Gene Ther. 2002 Apr;9(8):503-10. doi: 10.1038/sj.gt.3301677.

Abstract

Two vaccines against an intracellularly expressed B cell idiotype were assessed for their ability to induce protective immunity in mice against challenge with a pre-B cell leukemia. One vaccine was based on a plasmid expression vector and the other was a recombinant vaccinia virus; both vaccines expressed a polypeptide derived from the complementarity-determining regions (CDR(2)-CDR(3)) of the leukemic clone-specific immunoglobulin heavy chain (IgH), as a fusion product with mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF). Mice inoculated with either vaccine showed significantly higher survival rates than controls after challenge with leukemia cells. However, protection from tumor challenge was optimal when the DNA vaccine was used for priming, followed by a booster immunization with the vaccinia virus recombinant. This vaccination protocol induced resistance not only to the first tumor challenge given shortly afterwards, but also to a second challenge given months later. Both CD4(+) and CD8(+) T cells contributed to protection in vaccinated mice. These data suggest that such a vaccine regimen might reduce the incidence of recurrence in patients with minimal residual disease after conventional therapy.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Complementarity Determining Regions / genetics*
  • Female
  • Genetic Engineering
  • Genetic Vectors / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Immunoglobulin Heavy Chains / genetics*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Neoplasm, Residual / therapy*
  • Plasmids
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Recombinant Fusion Proteins / genetics
  • Vaccines, DNA / administration & dosage*
  • Vaccinia / genetics

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Granulocyte-Macrophage Colony-Stimulating Factor