CAR-T Meeting 2025 | The mechanisms of cardiotoxicity following treatment with CAR-T
In this video, Roni Shouval, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the mechanisms of CAR T-cell therapy-associated cardiotoxicity, highlighting three potential pathways leading to this complication. These include on-target off-tumor effects, where CAR T-cells target shared antigens between tumor and cardiac tissue, and off-target off-tumor effects, where CAR T-cells exhibit cross-reactivity with antigens on cardiac myocytes. This interview took place at the EHA-EBMT 7th European CAR T-cell Meeting, held in Strasbourg, France.
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Transcript (AI-generated)
When considering CAR T-cell-associated cardiotoxicity, we can think of three main mechanisms. One is related to cytokine release syndrome or CRS. We know that most cardiac adverse events happen in the setting of CRS, and we think that as part of the inflammatory reaction, there are secreted some inflammatory mediators such as IL-6, TNF-alpha, which can cause cardiac suppression and cardiac toxicity...
When considering CAR T-cell-associated cardiotoxicity, we can think of three main mechanisms. One is related to cytokine release syndrome or CRS. We know that most cardiac adverse events happen in the setting of CRS, and we think that as part of the inflammatory reaction, there are secreted some inflammatory mediators such as IL-6, TNF-alpha, which can cause cardiac suppression and cardiac toxicity. The two other potential mechanisms are one, what we call on-target off-tumor effects, where there is an antigen on cardiac tissue that is shared by the tumor and which is also the target of the CAR T-cell itself. This is more of a theoretical concern. It hasn’t been really shown in the CAR T-cell setting. But the third potential mechanism is what we call off-target, off-tumor effects of the CAR T-cells, where there could be cross-reactivity between the antigen that the CAR T-cells are targeting and a different antigen on the myocytes or the cardiac myocytes. And there is an example specifically in a TCR designed against a MAGE antigen, which had some cross-reactivity with a protein called titin, which is expressed on cardiac myocytes, and that caused two cases, unfortunately, of fulminant myocarditis.
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Disclosures
Speaker Honorarium from Incyte.
