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Editorial
. 2022 Dec 20;4(5):704-707.
doi: 10.1016/j.jaccao.2022.11.005. eCollection 2022 Dec.

Immune Checkpoint Inhibitor Myocarditis Treatment Strategies and Future Directions

Javid Moslehi  1 , Joe-Elie Salem  2
Affiliations
Editorial

Immune Checkpoint Inhibitor Myocarditis Treatment Strategies and Future Directions

Javid Moslehi et al. JACC CardioOncol. .
No abstract available

Keywords: CD86RO, cluster of differentiation 86 receptor occupancy; CTLA-4, cytotoxic T-lymphocyte antigen; ICI, immune checkpoint inhibitor; JAK, Janus kinase; MACE, major adverse cardiac event; PD-1, programmed cell death 1 receptor; abatacept; immunotherapy; lung cancer; myocarditis; pharmacology.

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Conflict of interest statement

Dr Moslehi is supported by National Institutes of Health grants (R01HL141466, R01HL155990, R01HL156021, and R01HL160688); and has served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Takeda, AstraZeneca, Heat Biologics, Incyte, Vertex, Verastem Oncology, Acceleron Pharmaceuticals, GlaxoSmithKline, TripleGene LLC, Regeneron, Nektar Therapeutics, Boston Biomedical, ImmunoCore, Janssen, Myovant, Silverback Therapeutics, Amgen, Kurome Therapeutics, Kiniksa Pharmaceuticals, Daiichi Sankyo, CRC Oncology, BeiGene, Star Therapeutics, ProteinQure, Pharmacyclics, Kiniksa, Prelude Therapeutics Mallinckrodt Pharmaceuticals, Boehringer, TransThera Sciences, Antev Ltd, IQVIA, AskBio, Lapcorp, Paladin, Quell Therapeutics, Voyager Therapeutics, CRC Oncology, and Cytokinetics. Dr Moslehi and Salem have patents pending related to the treatment of immune-related adverse events including ICI myocarditis.

Figures

None
Graphical abstract
Figure 1
Figure 1
Mechanism of Action of Approved Immune Checkpoint Agents (A) T-cell activation or anergy is mediated by a complex interaction between antigen-presenting cells (APCs) (eg, macrophages) and organ or tumor cells. The first step (1st signal) of T-cell immune activation against liable cells relies on the presentation of a culprit antigen by the APCs (major histocompatibility complex [MHC] class II) to T cells through the T-cell receptor (TCR). For complete activation (2nd signal), CD28 (on T cells) needs to bind with CD80/86 on the APC side. Notably, cytotoxic T-lymphocyte antigen 4 (CTLA-4) (on T cells) has a higher affinity for CD80/86 than for CD28, impeding CD28-CD80/86 interaction and toning down T-cell activation. When exposed to CTLA-4 blockers, CD28-CD80/86 binding and T-cell activation are facilitated. CTLA-4 fusion protein (eg, abatacept) has opposite effects. (B) A scheme of the ongoing phase II ACHLYS trial (NCT05195645), seeking to define the optimal abatacept dose to be used in ICI myocarditis to achieve a prompt and strong blockade (receptor occupancy, RO) of its target (CD86) on circulating monocytes (ie, CD86RO ≥ 80%). Ag, antigen; CTLA-4, cytotoxic T-lymphocyte antigen 4; LAG-3, lymphocyte-activation gene 3; PD-1, programmed cell death 1 receptor; PD-L1, programmed death 1 ligand.
See this image and copyright information in PMC

References

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