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Proc Natl Acad Sci U S A ; 104(21): 8947-52, 2007 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-17517626

RESUMO

The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.


Assuntos
Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/imunologia , Manitol/análogos & derivados , Proteínas de Membrana/imunologia , Ácidos Oleicos/imunologia , Oligodesoxirribonucleotídeos/imunologia , Células Th1/imunologia , Antígenos de Neoplasias/efeitos adversos , Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/uso terapêutico , Vacinas Anticâncer/imunologia , Epitopos de Linfócito B/imunologia , Humanos , Imunoterapia/efeitos adversos , Manitol/efeitos adversos , Manitol/sangue , Manitol/imunologia , Manitol/uso terapêutico , Proteínas de Membrana/efeitos adversos , Proteínas de Membrana/sangue , Proteínas de Membrana/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ácidos Oleicos/efeitos adversos , Ácidos Oleicos/sangue , Ácidos Oleicos/uso terapêutico , Oligodesoxirribonucleotídeos/efeitos adversos , Oligodesoxirribonucleotídeos/sangue , Oligodesoxirribonucleotídeos/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Vacinação
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