Can Culturing CAR T Cells With Ibrutinib Improve Their Efficacy in CLL?

This article was originally published by Cancer Therapy Advisor   

Efficacy of chimeric antigen receptor (CAR) T-cell (CAR-T) therapies in chronic lymphocytic leukemia (CLL) have lagged behind the efficacy they appear to have in other hematological malignancies such as acute lymphoblastic leukemia or diffuse large B-cell lymphoma.

There’s a growing recognition that some of the CAR-T shortfalls in CLL are due to an impaired fitness of T cells in CLL patients. Some research has shown, however, that sustained remission of CLL is associated with enrichment of a less-differentiated, early-memory phenotype of T cells in the apheresis product used to make CAR-T therapies.1 Such findings have galvanized interest in approaches to enhance this T-cell population during the immunotherapy manufacturing process as a possible route for overcoming treatment resistance.

Now, a small study in the International Journal of Cancer reported that culturing CLL patients’ T cells with the tyrosine kinase inhibitor ibrutinib — which among other effects, inhibits a pathway involved in T-cell differentiation — boosted the viability, function, and expansion of CLL patient-derived CAR T cells as well as enriching them with a less-differentiated phenotype.2

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