Augmentation Of Adoptive T-Cell Therapy For Merkel Cell Carcinoma With Avelumab.

JOURNAL OF CLINICAL ONCOLOGY(2017)

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摘要
3044Background: 80% of Merkel cell carcinomas (MCCs) are caused by Merkel cell polyomavirus (MCPyV) oncoproteins. Although absent in most cases, abundant MCPyV-specific CD8+ TIL are associated with good MCC outcomes, implying tumor susceptibility to immune attack. Indeed, anti-PD-1 axis blockade has a response rate of 32-56%. However, half of patients do not respond, suggesting a lack of adequate MCPyV-specific T cells and/or tumor evasion from MCC-related reduced HLA expression. We hypothesized the combination of adoptive transfer of MCPyV-specific T cells with HLA upregulation and PD1 axis blockade would be more effective than either approach alone. Methods: 8 adult patients with MCPyV-associated metastatic MCC without pre-existing immune deficiencies were enrolled. The safety and efficacy of ex vivo expanded MCPyV-specific T-cells plus HLA-upregulation (radiation or interferon) with (triple therapy) and without (double therapy) avelumab (mAb against PD-L1, dose 10 mg/kg IV q2weeks) were compared in 2 r...
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