Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors

Bone Marrow Transplant. 2010 Mar;45(3):550-7. doi: 10.1038/bmt.2009.185. Epub 2009 Aug 3.

Abstract

We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / genetics
  • Base Sequence
  • Bone Marrow Transplantation
  • CD40 Ligand / administration & dosage
  • CD40 Ligand / genetics
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cell Line, Tumor
  • DNA Primers / genetics
  • Genes, abl
  • Immunization, Secondary
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / immunology
  • Leukemia, Experimental / therapy*
  • Lymphocyte Depletion
  • Lymphopenia / etiology
  • Lymphopenia / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Whole-Body Irradiation

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA Primers
  • Recombinant Fusion Proteins
  • CD40 Ligand