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Graft-Versus-Tumor Effects

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

Bone Marrow Transplantation volume 45, pages 550–557 (2010)Cite this article

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.

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Acknowledgements

The SKCC and AD thank the Kaye and Richard Woltman Foundation for support of the development of post-allograft vaccination methods designed to reduce the post-allograft incidence of recurrence and opportunistic viral infections. AD recognizes support of the vaccine program from the Breast Cancer Research Foundation, the DOD (BCRP program (BC022063)), and a grant from the State of California Breast Cancer Research Program (CBCRP12IB-0159). Authors thank Dr Brian Druker for 32Dp210Bcrabl cells. Dr Tae Hae Han recognizes support from SBRI grant B-A7-204 and SRC grant from Korea Science and Engineering Foundation.

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Authors and Affiliations

  1. Department of Genetic Therapy, Sydney Kimmel Cancer Center, San Diego, CA, USA

    T H Han, Y Tang, Y H Park, J Maynard, P Li, H Akbulut, L Petersen & A Deisseroth

  2. Department of Molecular Cell Biology, Molecular Therapy Research Center, SBRI, Seoul, Korea

    T H Han

  3. Department of Hemato-oncology, Sungkyunkwan University School of Medicine, Suwon 440-746, and Samsung Medical Center, Seoul, Republic of Korea

    Y H Park

  4. Department of Medical Oncology of Ibni Sina Hospital of Ankara University, Ankara, Turkey

    H Akbulut

  5. Department of Immunology, Aahrus University, Aahrus, Denmark

    L Petersen

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  1. T H Han
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Correspondence to A Deisseroth.

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Han, T., Tang, Y., Park, Y. et al. Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors. Bone Marrow Transplant 45, 550–557 (2010). https://doi.org/10.1038/bmt.2009.185

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  • DOI: https://doi.org/10.1038/bmt.2009.185

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