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ICML 2025 | Mechanisms of resistance to T-cell redirecting therapies
In this video, Ash Alizadeh, MD, PhD, Stanford University, Stanford, CA, comments on the mechanisms of resistance to T-cell redirecting therapies, highlighting three key areas that are thought to influence whether these therapies are effective in patients. These include T-cell intrinsic factors, such as product expansion; tumor-related factors, including genetic mutations; and the tumor microenvironment, which influences the ability of T-cells to exert anti-tumor effects. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
So I think from a big picture I think less is known than is unknown but for the parts that we know about T-cell redirecting therapies we tend to break them up into at least the way I think about it three big groups of why the therapies work or don’t work. One is related to the products that we’re using, especially if they’re engineered therapies, where the product may or may not expand or things like that for CAR T-cells in particular...
So I think from a big picture I think less is known than is unknown but for the parts that we know about T-cell redirecting therapies we tend to break them up into at least the way I think about it three big groups of why the therapies work or don’t work. One is related to the products that we’re using, especially if they’re engineered therapies, where the product may or may not expand or things like that for CAR T-cells in particular. So that’s what we call T-cell intrinsic. The other is the tumor factors that might determine, let’s say, genetic mutations, the pattern of expression of the target and its tendency to be lost. And the third concept is the idea of the microenvironment, the niche, the environment in which these T-cells need to home and to do their anti-tumor effects if that microenvironment is hospitable or not hospitable. So those are the three big groups that I think about from conceptual terms.
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