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COMy 2026 | T-cell fitness and the tumor microenvironment in CAR T-cell therapy for myeloma
Nikhil Munshi, MD, Dana-Farber Cancer Institute, Boston, MA, discusses how T-cell characteristics and the tumor microenvironment influence responses to CAR T-cell therapy in multiple myeloma. He reviews the role of T-cell fitness, expansion, memory phenotypes, and immune cell interactions in determining efficacy and toxicity, highlighting emerging strategies to optimize CAR T-cell outcomes. This interview took place at the 12th World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.
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Transcript
So what is becoming important in immunology is that when we give CAR T-cells, and similarly for bispecific, the T-cells that are infused in the patient and its characteristics, its function, plays a very important role in providing us response and also duration of response. So patients can do well for a long period. And in our analysis of the paper, which was published by Dr. Merz and his group in Cell, we looked at all the data presented there as well as in the literature and have summarized that it’s not just the T-cell but there are a number of features which influence how patients do following CAR T-cell...
So what is becoming important in immunology is that when we give CAR T-cells, and similarly for bispecific, the T-cells that are infused in the patient and its characteristics, its function, plays a very important role in providing us response and also duration of response. So patients can do well for a long period. And in our analysis of the paper, which was published by Dr. Merz and his group in Cell, we looked at all the data presented there as well as in the literature and have summarized that it’s not just the T-cell but there are a number of features which influence how patients do following CAR T-cell. Now the easiest target is the patient’s T-cell obtained before the CAR T-cells are produced, it’s health is very important. So patients should not receive certain treatments which may impact the T-cell function. So the characteristics of collection play an important role. The CAR T-cell product in turn plays an important role. And then what came about is that once the CAR T-cells are infused, the T-cell expansion in the patient and its characteristics, whether they have effector memory phenotype or central memory phenotype, is important and if it is CD4 CAR T-cells or CD8 CAR T-cells is critically important; there’s a recent publication that shows that CD4 CAR T-cells are important for response, but are also responsible for causing toxicity, for example, enteritis. And so now we can begin to consider, can we do without certain types of cells? And that’s for the future. Also, there are other components; there are macrophages, there are NK cells; each of them plays a role in influencing the tumor microenvironment and providing us responses or duration of responses that may be favorable or in some cases it can inhibit that, so this whole cellular orchestra, not just played by CAR T-cells, but CAR T-cells in conjunction with the tumor cell and the bone marrow microenvironmental cells, plays a critical role in defining this and then influencing them by either therapy, by giving cytokines, or by depleting some other cells, might provide us with the best response and, in turn, decreasing toxicity.
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