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Med Sci (Paris). 2019 Dec;35(12):966-974. doi: 10.1051/medsci/2019193. Epub 2020 Jan 6.

[Next generation of anti-immune checkpoints antibodies].

[Article in French; Abstract available in French from the publisher]

Author information

1
IRCM, Inserm, Université de Montpellier, ICM, Montpellier, F-34298 France.
2
Centre de recherche en cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR 7258, Aix-Marseille Université et Institut Paoli-Calmettes, Marseille, France.
3
Centre de recherche en transplantation et immunologie (CRTI) UMR1064, Inserm, Université de Nantes, Nantes, 44093, France.

Abstract

in English, French

Immune checkpoints balance initial antigen-driven T cell stimulation by enhancing or dampening activation, allowing co-existence of efficient immune responses and maintenance of self-tolerance. In oncology, checkpoints currently targeted by inhibitors to amplify activity of T cell, NK cells or myeloid cells responses comprise CTLA-4 (cytolytic T-lymphocyte-associated antigen 4 or CD152), PD-1 (programmed cell death 1, or CD279), PD-L1 ( programmed cell death-ligand 1, or CD274), LAG-3 (Lymphocyte-activation gene 3, or CD223), TIM3 (T-cell immunoglobulin and mucin-domain containing-3), TIGIT (T cell immunoreceptor with Ig and ITIM domains ), VISTA (V-domain Ig suppressor of T cell activation), B7/H3 (or CD276), KIR (killer-cell immunoglobulin-like receptor), NKG2A, CD39, CD73, CSF1R (colony-stimulating factor 1 receptor), CD47 or CD172a. Other "checkpoints" are being pharmacologically triggered in order to directly amplify T cell co-stimulation. Among these molecules, CD28, CD137 (also called 4-1BB), OX40 [also called tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], GITR (Glucocorticoid-induced tumor necrosis factor receptor family-related protein) or CD40 are also tested in oncology, most often in combination with an inhibitory checkpoint inhibitor. In autoimmune and inflammatory diseases, checkpoint inhibitors or activators (LAG-3, CD28, CD40L) are also being tested. In this review, we focus on some modulators of immune checkpoints for which the mechanism of action has been particularly studied. As this description cannot be exhaustive, we have grouped in Table I all monoclonal antibodies (MAbs) or recombinant proteins in clinical use (to our knowledge), modulating the action of a control point of the immune system.

PMID:
31903901
DOI:
10.1051/medsci/2019193

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