Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors.
J Clin Invest
; 109(5): 651-9, 2002 Mar.
Article
em En
| MEDLINE
| ID: mdl-11877473
ABSTRACT
Treatment of advanced, poorly immunogenic tumors in animal models, considered the closest simulation available thus far for conditions observed in cancer patients, remains a major challenge for cancer immunotherapy. We reported previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen-specific cytotoxic T lymphocyte responses. In this study, we demonstrate that several poorly immunogenic tumors, including C3 tumor, TC-1 lung carcinoma, and B16-F10 melanoma, once established as solid tumors or metastases, are refractory to treatment by anti-4-1BB mAb. We provide evidence that immunological ignorance, rather than anergy or deletion, of tumor antigen--specific CTLs during the progressive growth of tumors prevents costimulation by anti-4-1BB mAb. Breaking CTL ignorance by immunization with a tumor antigen-derived peptide, although insufficient to stimulate a curative CTL response, is necessary for anti--4-1BB mAb to induce a CTL response leading to the regression of established tumors. Our results suggest a new approach for immunotherapy of human cancers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Fator de Crescimento Neural
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Receptores do Fator de Necrose Tumoral
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Imunoterapia
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Antígenos de Neoplasias
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Neoplasias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos