Pular para o conteúdo
Merck

Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.

Science translational medicine (2014-09-19)
Pia Kvistborg, Daisy Philips, Sander Kelderman, Lois Hageman, Christian Ottensmeier, Deborah Joseph-Pietras, Marij J P Welters, Sjoerd van der Burg, Ellen Kapiteijn, Olivier Michielin, Emanuela Romano, Carsten Linnemann, Daniel Speiser, Christian Blank, John B Haanen, Ton N Schumacher
RESUMO

Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whether treatment amplifies previously induced T cell responses or whether it induces new tumor-specific T cell reactivities. Using a combination ultraviolet (UV)-induced peptide exchange and peptide-major histocompatibility complex (pMHC) combinatorial coding, we monitored immune reactivity against a panel of 145 melanoma-associated epitopes in a cohort of patients receiving anti-CTLA-4 treatment. Comparison of pre- and posttreatment T cell reactivities in peripheral blood mononuclear cell samples of 40 melanoma patients demonstrated that anti-CTLA-4 treatment induces a significant increase in the number of detectable melanoma-specific CD8 T cell responses (P = 0.0009). In striking contrast, the magnitude of both virus-specific and melanoma-specific T cell responses that were already detected before start of therapy remained unaltered by treatment (P = 0.74). The observation that anti-CTLA-4 treatment induces a significant number of newly detected T cell responses-but only infrequently boosts preexisting immune responses-provides strong evidence for anti-CTLA-4 therapy-enhanced T cell priming as a component of the clinical mode of action.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Brefeldina A, from Penicillium brefeldianum, ≥99% (HPLC and TLC)
Sigma-Aldrich
Brefeldina A, ≥99% (HPLC and TLC), BioXtra, for molecular biology
Sigma-Aldrich
Brefeldina A, from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO