Enhancement of graft-versus-tumor activity and graft-versus-host disease by pretransplant immunization of allogeneic bone marrow donors with a recipient-derived tumor cell vaccine

Larry D. Anderson, Demetrios Petropoulos, Linda A. Everse, Craig A. Mullen

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Abstract

Allogeneic bone marrow transplantation (BMT) can be accompanied by a beneficial T cell-mediated antitumor immune response known as graft-versus- tumor (GVT) activity. However, BMT donor T cells are not exposed to target antigens of GVT activity until transfer to the host, where tumor antigen presentation may be suboptimal. This study tested in a murine model the hypothesis that immunization of MHC-matched allogeneic donors with a recipient-derived tumor cell vaccine would substantially increase GVT activity and extend survival of BMT recipients with preexisting micrometastatic tumor. C3H.SW and C57BL/10 mice were immunized against a C57BL/6-derived fibrosarcoma or leukemia, and they were used as BMT donors. Recipients were H-2-matched, minor histocompatibility antigen-mismatched C57BL/6 mice with previously established micrometastatic tumors. Donor immunization led to a significant increase in GVT activity that was T cell dependent and cell dose dependent. In some settings, donor immunization also prolonged survival of recipients with preexisting micrometastatic tumors. However, donor immunization significantly increased the incidence of fatal graft-versus-host disease such that long-term survival was uncommon. In vitro cytotoxicity assays indicated that donor immunization induced both tumor- selective and alloreactive cytolytic T-cell populations. In vivo cross- protection assays showed that a substantial portion of the GVT effect was mediated by alloreactive cells not specific for the immunizing tumor. In conclusion, immunization of allogeneic BMT donors with a recipient-derived whole tumor cell vaccine substantially increases GVT activity but also exacerbates graft-versus-host disease.

Original languageEnglish (US)
Pages (from-to)1525-1530
Number of pages6
JournalCancer Research
Volume59
Issue number7
StatePublished - Apr 1 1999

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Immunologic Graft Enhancement
Cancer Vaccines
Graft vs Host Disease
Immunization
Bone Marrow
Bone Marrow Transplantation
Neoplasms
Transplants
T-Lymphocytes
Homologous Transplantation
Inbred C57BL Mouse
Minor Histocompatibility Antigens
Cross Protection
Fibrosarcoma
Antigen Presentation
Neoplasm Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Enhancement of graft-versus-tumor activity and graft-versus-host disease by pretransplant immunization of allogeneic bone marrow donors with a recipient-derived tumor cell vaccine. / Anderson, Larry D.; Petropoulos, Demetrios; Everse, Linda A.; Mullen, Craig A.

In: Cancer Research, Vol. 59, No. 7, 01.04.1999, p. 1525-1530.

Research output: Contribution to journalArticle

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