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Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 7/2/2024, Vol. 121 Issue 27, p1-7, 15p
- Publication Year :
- 2024
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 121
- Issue :
- 27
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 178326909
- Full Text :
- https://doi.org/10.1073/pnas.2404661121