Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease

Larry D. Anderson, Cherylyn A. Savary, Craig A. Mullen

Research output: Contribution to journalArticle

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Abstract

Allogeneic bone marrow transplantation (BMT) induces 2 closely associated immune responses: graft-versus-tumor (GVT) activity and graft- versus-host disease (GVHD). We have previously shown that pretransplant immunization of allogeneic BMT donors with a recipient-derived tumor cell vaccine increases both GVT activity and lethal GVHD because of the priming of donor T cells against putative minor histocompatibility antigens (mHAgs) on the tumor vaccine cells. The work reported here tested the hypothesis that tumor cell vaccination after BMT would produce an increase in GVT activity without exacerbating GVHD. C3H.SW donor bone marrow and splenocytes were transplanted into major histocompatibility complex-matched, mHAg-mismatched C57BL/6 recipients. One month after BMT, recipients were immunized against either a C57BL/6 myeloid leukemia (C1498) or fibrosarcoma (205). Immunized recipients had a significant increase in survival and protection against tumor growth In both tumor models, and significant tumor protection was seen even in recipients with preexisting micrometastatic cancer before immunization. Alloreactivity appeared to contribute to the in vitro anti- tumor cytolytic activity, but in vivo immunity was tumor specific, and no exacerbation of GVHD was observed. Although the immunodominant mHAg B6(dom1) was shown to be expressed by all B6 tumors tested and was largely responsible for the alloreactivity resulting from tumor immunization of donors, the in vitro alloreactivity of immune recipients was more restricted and was not mediated by recognition of B6d(dom1). In conclusion, post-transplant tumor immunization of allogeneic BMT recipients against either a leukemia or a solid tumor can increase GVT activity and survival without exacerbating GVHD. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2426-2433
Number of pages8
JournalBlood
Volume95
Issue number7
StatePublished - Apr 1 2000

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Immunization
Transplants
Cancer Vaccines
Graft vs Host Disease
Grafts
Tumors
Bone
Vaccines
Bone Marrow
Cells
Neoplasms
Bone Marrow Transplantation
Transplantation (surgical)
Homologous Transplantation
Tissue Donors
Transplant Recipients
Minor Histocompatibility Antigens
Myeloid Leukemia
T-cells
Fibrosarcoma

ASJC Scopus subject areas

  • Hematology

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Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. / Anderson, Larry D.; Savary, Cherylyn A.; Mullen, Craig A.

In: Blood, Vol. 95, No. 7, 01.04.2000, p. 2426-2433.

Research output: Contribution to journalArticle

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