Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy.

Autor:	Mok S; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030., Ağaç Çobanoğlu D; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030., Liu H; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030., Mancuso JJ; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.; Parker Institute for Cancer Immunotherapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030., Allison JP; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.; Parker Institute for Cancer Immunotherapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 02; Vol. 121 (27), pp. e2404661121. Date of Electronic Publication: 2024 Jun 26.
DOI:	10.1073/pnas.2404661121
Abstrakt:	Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy. Competing Interests: Competing interests statement:J.P.A. reports consulting, advisory roles, and/or stocks/ownership for Achelois, Adaptive Biotechnologies, Akoya Biosciences, Apricity, Bectas, BioAtla, BioNTech, Candel Therapeutics, Dragonfly, Earli, Enable Medicine, Hummingbird, ImaginAb, Lava Therapeutics, Lytix, Marker, Osteologic, PBM Capital, Phenomic AI, Polaris Pharma, Time Bioventures, Trained Therapeutix, Two Bear Capital, and Venn Biosciences.
Databáze:	MEDLINE
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