Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanomaReportar como inadecuado




Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Translational Medicine

, 6:22

First Online: 01 May 2008Received: 31 January 2008Accepted: 01 May 2008DOI: 10.1186-1479-5876-6-22

Cite this article as: Comin-Anduix, B., Lee, Y., Jalil, J. et al. J Transl Med 2008 6: 22. doi:10.1186-1479-5876-6-22

Abstract

BackgroundCTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated.

MethodsPeripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab formerly CP-675,206 at 10 mg-kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1 tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2 activation HLA-DR and memory CD45RO markers on CD4-CD8 cells; and 3 real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis.

ResultsThree of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8 cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup.

ConclusionAdministration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood.

Clinical trial registration numberNCT00086489

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-6-22 contains supplementary material, which is available to authorized users.

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Autor: Begoña Comin-Anduix - Yohan Lee - Jason Jalil - Alain Algazi - Pilar de la Rocha - Luis H Camacho - Viviana A Bozon - Ce

Fuente: https://link.springer.com/







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