Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation
Allogeneic bone marrow transplantation is currently restricted to hematological malignancies because of a lack of anti-tumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific anti-tumor activity against a solid tumor after transplantation by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor. Using the B16 melanoma model, we found that vaccination elicited potent anti-tumor activity in recipients of syngeneic bone marrow transplantation in a time dependent fashion, and that immune reconstitution was critical for the development of anti-tumor activity. Vaccination did not stimulate anti-tumor immunity after allogeneic bone marrow transplantation because of the post-transplantation immunodeficiency associated with graft-versus-host disease. Remarkably, vaccination was effective in stimulating potent and long-lasting anti-tumor activity in recipients of T cell-depleted allogeneic bone marrow. Thus T cells derived from donor stem cells were able to recognize tumor antigens even though they remained tolerant to host histocompatibility antigens. Donor leukocyte infusion from a donor immunized with the recipient-derived B16 vaccines enhanced clinical activity of tumor vaccines without exacerbating graft-versus-host disease and CD4+ T cells are essential for this enhancement. These results demonstrate that vaccination of both donors and recipients can stimulate potent anti-tumor effects without the induction of graft-versus-host disease, and this strategy has important implications for the treatment of patients with solid malignancies.
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Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
2002
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oai:scielo:S1516-848420020003000112003-01-14Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantationFerrara,James L.M. Granulocyte-macrophage colony-stimulating factor bone marrow transplantation graft-versus-host disease graft-versus-tumor cancer vaccination T cell-depletion donor leukocyte infusions Allogeneic bone marrow transplantation is currently restricted to hematological malignancies because of a lack of anti-tumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific anti-tumor activity against a solid tumor after transplantation by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor. Using the B16 melanoma model, we found that vaccination elicited potent anti-tumor activity in recipients of syngeneic bone marrow transplantation in a time dependent fashion, and that immune reconstitution was critical for the development of anti-tumor activity. Vaccination did not stimulate anti-tumor immunity after allogeneic bone marrow transplantation because of the post-transplantation immunodeficiency associated with graft-versus-host disease. Remarkably, vaccination was effective in stimulating potent and long-lasting anti-tumor activity in recipients of T cell-depleted allogeneic bone marrow. Thus T cells derived from donor stem cells were able to recognize tumor antigens even though they remained tolerant to host histocompatibility antigens. Donor leukocyte infusion from a donor immunized with the recipient-derived B16 vaccines enhanced clinical activity of tumor vaccines without exacerbating graft-versus-host disease and CD4+ T cells are essential for this enhancement. These results demonstrate that vaccination of both donors and recipients can stimulate potent anti-tumor effects without the induction of graft-versus-host disease, and this strategy has important implications for the treatment of patients with solid malignancies.info:eu-repo/semantics/openAccessAssociação Brasileira de Hematologia e Hemoterapia e Terapia CelularRevista Brasileira de Hematologia e Hemoterapia v.24 n.3 20022002-01-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011en10.1590/S1516-84842002000300011 |
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Ferrara,James L.M. |
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Ferrara,James L.M. Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
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Ferrara,James L.M. |
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Ferrara,James L.M. |
title |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
title_short |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
title_full |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
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Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
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Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
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tumor vaccine strategies after allogeneic t-cell depleted bone marrow transplantation |
description |
Allogeneic bone marrow transplantation is currently restricted to hematological malignancies because of a lack of anti-tumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific anti-tumor activity against a solid tumor after transplantation by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor. Using the B16 melanoma model, we found that vaccination elicited potent anti-tumor activity in recipients of syngeneic bone marrow transplantation in a time dependent fashion, and that immune reconstitution was critical for the development of anti-tumor activity. Vaccination did not stimulate anti-tumor immunity after allogeneic bone marrow transplantation because of the post-transplantation immunodeficiency associated with graft-versus-host disease. Remarkably, vaccination was effective in stimulating potent and long-lasting anti-tumor activity in recipients of T cell-depleted allogeneic bone marrow. Thus T cells derived from donor stem cells were able to recognize tumor antigens even though they remained tolerant to host histocompatibility antigens. Donor leukocyte infusion from a donor immunized with the recipient-derived B16 vaccines enhanced clinical activity of tumor vaccines without exacerbating graft-versus-host disease and CD4+ T cells are essential for this enhancement. These results demonstrate that vaccination of both donors and recipients can stimulate potent anti-tumor effects without the induction of graft-versus-host disease, and this strategy has important implications for the treatment of patients with solid malignancies. |
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Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular |
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2002 |
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http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011 |
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AT ferrarajameslm tumorvaccinestrategiesafterallogeneictcelldepletedbonemarrowtransplantation |
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1756423378154029056 |