Adoptive T-cell Transfer Therapy and Oncogene-Targeted Therapy for Melanoma: The Search for Synergy.

Adoptive T-cell Transfer Therapy and Oncogene-Targeted Therapy for Melanoma: The Search for Synergy. Clin Cancer Res. 2013 Oct 1;19(19):5292-5299 Authors: Kwong ML, Neyns B, Yang JC Abstract The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib w...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research