Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation
Autor(a) principal: | |
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Data de Publicação: | 2002 |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Revista brasileira de hematologia e hemoterapia (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011 |
Resumo: | 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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Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantationGranulocyte-macrophage colony-stimulating factorbone marrow transplantationgraft-versus-host diseasegraft-versus-tumorcancer vaccinationT cell-depletiondonor leukocyte infusionsAllogeneic 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.Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular2002-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011Revista Brasileira de Hematologia e Hemoterapia v.24 n.3 2002reponame:Revista brasileira de hematologia e hemoterapia (Online)instname:Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC)instacron:ABHHTC10.1590/S1516-84842002000300011info:eu-repo/semantics/openAccessFerrara,James L.M.eng2003-01-14T00:00:00Zoai:scielo:S1516-84842002000300011Revistahttp://www.rbhh.org/pt/archivo/https://old.scielo.br/oai/scielo-oai.phpsbhh@terra.com.br||secretaria@rbhh.org1806-08701516-8484opendoar:2003-01-14T00:00Revista brasileira de hematologia e hemoterapia (Online) - Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC)false |
dc.title.none.fl_str_mv |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
title |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
spellingShingle |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation Ferrara,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 |
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 |
title_fullStr |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
title_full_unstemmed |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
title_sort |
Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation |
author |
Ferrara,James L.M. |
author_facet |
Ferrara,James L.M. |
author_role |
author |
dc.contributor.author.fl_str_mv |
Ferrara,James L.M. |
dc.subject.por.fl_str_mv |
Granulocyte-macrophage colony-stimulating factor bone marrow transplantation graft-versus-host disease graft-versus-tumor cancer vaccination T cell-depletion donor leukocyte infusions |
topic |
Granulocyte-macrophage colony-stimulating factor bone marrow transplantation graft-versus-host disease graft-versus-tumor cancer vaccination T cell-depletion donor leukocyte infusions |
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. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842002000300011 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S1516-84842002000300011 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular |
publisher.none.fl_str_mv |
Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular |
dc.source.none.fl_str_mv |
Revista Brasileira de Hematologia e Hemoterapia v.24 n.3 2002 reponame:Revista brasileira de hematologia e hemoterapia (Online) instname:Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC) instacron:ABHHTC |
instname_str |
Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC) |
instacron_str |
ABHHTC |
institution |
ABHHTC |
reponame_str |
Revista brasileira de hematologia e hemoterapia (Online) |
collection |
Revista brasileira de hematologia e hemoterapia (Online) |
repository.name.fl_str_mv |
Revista brasileira de hematologia e hemoterapia (Online) - Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC) |
repository.mail.fl_str_mv |
sbhh@terra.com.br||secretaria@rbhh.org |
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1754213107532562432 |