Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma.
Clin Cancer Res
; 15(19): 6267-76, 2009 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-19789309
ABSTRACT
PURPOSE:
Tumor antigen-loaded dendritic cells (DC) are believed to activate antitumor immunity by stimulating T cells, and CTL-associated antigen 4 (CTLA4)-blocking antibodies should release a key negative regulatory pathway on T cells. The combination was tested in a phase I clinical trial in patients with advanced melanoma. EXPERIMENTALDESIGN:
Autologous DC were pulsed with MART-1(26-35) peptide and administered with a dose escalation of the CTLA4-blocking antibody tremelimumab. Sixteen patients were accrued to five dose levels. Primary end points were safety and immune effects; clinical efficacy was a secondary end point.RESULTS:
Dose-limiting toxicities of grade 3 diarrhea and grade 2 hypophysitis developed in two of three patients receiving tremelimumab at 10 mg/kg monthly. Four patients had an objective tumor response, two partial responses and two complete responses, all melanoma free between 2 and 4 years after study initiation. There was no difference in immune monitoring results between patients with an objective tumor response and those without a response. Exploratory gene expression analysis suggested that immune-related gene signatures, in particular for B-cell function, may be important in predicting response.CONCLUSION:
The combination of MART-1 peptide-pulsed DC and tremelimumab results in objective and durable tumor responses at the higher range of the expected response rate with either agent alone.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Antígenos CD
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Imunoterapia Adotiva
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Anticorpos Bloqueadores
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Vacinas Anticâncer
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Melanoma
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article