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Clin Cancer Res. 2009 Oct 1;15(19):6267-76. doi: 10.1158/1078-0432.CCR-09-1254. Epub 2009 Sep 29.

Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma.

Author information

1
Department of Medicine, Division of Hematology/Oncology, University of California at Los Angeles, Los Angeles, California 90095-1782, USA. aribas@mednet.ucla.edu

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.

EXPERIMENTAL DESIGN:

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.

PMID:
19789309
PMCID:
PMC2765061
DOI:
10.1158/1078-0432.CCR-09-1254
[Indexed for MEDLINE]
Free PMC Article

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