ASH 2023 | T-cell engagers vs monoclonal antibodies for the treatment of AML: the influence of CD38 expression
Aintzane Zabaleta, University of Navarra, Pamplona, Spain, highlights findings which suggest that trispecific CD38/CD28xCD3 T-cell engagers (TCEs) may hold potential for treating older patients with acute myeloid leukemia (AML). The heterogeneity of CD38 expression on blasts of AML patients means that monoclonal antibody treatments have limited efficacy in those patients with lower expression. In contrast, CD38 density has not been found to be a factor affecting the anti-tumor efficacy of TCE treatment. However, further investigation is needed to fully understand the mechanisms of action underlying this finding. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
This trispecific molecule is being developed by Sanofi and it’s intended to be used for the treatment of multiple myeloma patients, but we’ve been also testing this molecule in the context of AML in older patients. Our idea was, since AML blasts express CD38, they might be targeted with this molecule. The problem in AML is that the expression levels of C38 are not as high as in multiple myeloma, and with monoclonal antibodies, what we have observed is that the density of target molecules on the surface of tumor cells is something to take into account in order to see a therapeutic effect...
This trispecific molecule is being developed by Sanofi and it’s intended to be used for the treatment of multiple myeloma patients, but we’ve been also testing this molecule in the context of AML in older patients. Our idea was, since AML blasts express CD38, they might be targeted with this molecule. The problem in AML is that the expression levels of C38 are not as high as in multiple myeloma, and with monoclonal antibodies, what we have observed is that the density of target molecules on the surface of tumor cells is something to take into account in order to see a therapeutic effect. So, with T-cell engagers, it’s true that the density is not as important. It’s true that it has something to do, and with higher expression we are seeing better response, but it’s not as important as for monoclonal antibodies. And we’ve been testing how these therapeutic compounds could act in this setting in AML. And we are seeing that we are able to see some efficacy, but I think that in this case, we would need to analyze more samples and study more carefully the mechanisms of actions that are triggered. We are seeing that it’s mediated by T-cells. It’s promising, but we need to continue working on that.
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