Ibrutinib for improved chimeric antigen receptor T-cell production for chronic lymphocytic leukemia patients.

International Journal of Cancer. Journal International Du Cancer
Fuli FanLeopold Sellner

Abstract

Chimeric antigen receptor T (CART) cells targeting CD19 have shown promising results in the treatment of chronic lymphocytic leukemia (CLL). However, efficacy seems to be inferior compared to diffuse large B-cell lymphoma or acute lymphoblastic leukemia. Impaired T-cell fitness of CLL patients may be involved in treatment failure. Less-differentiated naïve-like T cells play an important role in CART expansion and long-term persistence in vivo. These cells are sparse in CLL patients. Therefore, optimization of CART cell production protocols enriching less differentiated T cell subsets may overcome treatment resistance. The B-cell receptor inhibitor ibrutinib targeting Bruton's tyrosine kinase (BTK) is approved for the treatment of CLL. Besides BTK, ibrutinib additionally inhibits interleukin-2-inducible T-cell kinase (ITK) which is involved in T-cell differentiation. To evaluate the effect of ibrutinib on CART cell production, peripheral blood mononuclear cells from nine healthy donors and eight CLL patients were used to generate CART cells. T-cell expansion and phenotype, expression of homing and exhaustion makers as well as functionality of CART cells were evaluated. CART cell generation in the presence of ibrutinib resulted i...Continue Reading

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Dec 29, 2020·Clinical Lymphoma, Myeloma & Leukemia·Solomon A GrafAjay K Gopal
Jun 8, 2021·Current Treatment Options in Oncology·Katherine HarrisMichael R Bishop
Aug 10, 2021·IScience·Samuel WeeksMobin Karimi

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