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Abstract:

Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8 + T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180-188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice.

Registro:

Documento: Artículo
Título:Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
Autor:Goldszmid, R.S.; Idoyaga, J.; Bravo, A.I.; Steinman, R.; Mordoh, J.; Wainstok, R.
Filiación:Instituto Leloir, Inst. Invest. Bioquim. Buenos Aires, Buenos Aires, Argentina
Departamento de Quimica Biologica, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Hospital Eva Perón, San Martín, Buenos Aires, Argentina
Lab. of Cell. Physiol. and Immunol., Rockefeller University, 1230 York Avenue, New York, NY 10021, United States
Palabras clave:CD4 antigen; CD8 antigen; gamma interferon; major histocompatibility antigen class 1; tyrosinase related protein 2; animal cell; animal experiment; animal model; antigen expression; antigen recognition; apoptosis; article; bone marrow cell; cell culture; cell maturation; cell migration; cell stimulation; cellular immunity; coculture; controlled study; cytokine release; cytolysis; dendritic cell; experiment; immunogenicity; in vitro study; in vivo study; injection; inoculation; lymph node; lymphatic drainage; lymphocyte depletion; male; melanoma cell; mouse; nonhuman; priority journal; protein expression; provocation test; T lymphocyte; target cell; tumor cell; tumor immunity; vaccination
Año:2003
Volumen:171
Número:11
Página de inicio:5940
Página de fin:5947
DOI: http://dx.doi.org/10.4049/jimmunol.171.11.5940
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:gamma interferon, 82115-62-6
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00221767_v171_n11_p5940_Goldszmid.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n11_p5940_Goldszmid

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Citas:

---------- APA ----------
Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J. & Wainstok, R. (2003) . Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma. Journal of Immunology, 171(11), 5940-5947.
http://dx.doi.org/10.4049/jimmunol.171.11.5940
---------- CHICAGO ----------
Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J., Wainstok, R. "Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma" . Journal of Immunology 171, no. 11 (2003) : 5940-5947.
http://dx.doi.org/10.4049/jimmunol.171.11.5940
---------- MLA ----------
Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J., Wainstok, R. "Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma" . Journal of Immunology, vol. 171, no. 11, 2003, pp. 5940-5947.
http://dx.doi.org/10.4049/jimmunol.171.11.5940
---------- VANCOUVER ----------
Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J., Wainstok, R. Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma. J. Immunol. 2003;171(11):5940-5947.
http://dx.doi.org/10.4049/jimmunol.171.11.5940