Development of universal CAR-T cells].

Yuki Kagoya, Naoto Hirano

[Rinsho ketsueki] The Japanese journal of clinical hematology 2022

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The efficacy of adoptive immunotherapy using CD19-targeting chimeric antigen receptor (CAR)-engineered T cells against B-cell malignancies has already been established in the clinic. However, high economic costs and heterogeneous quality of CAR-T cells derived from individual patients hinder further expansion of their applicability to various cancer types, including solid tumors. Mass CAR-T cell production from healthy donors is a promising approach to overcome these problems, given that allogeneic immunity elicited against donor CAR-T cells by the recipient's immune system is controlled. CAR-T cells genetically ablated with T-cell receptor and human leukocyte antigen molecules, referred to as universal CAR-T cells, may enable the use of allogeneic T cells for off-the-shelf adoptive cancer immunotherapy. However, several concerns, such as poor persistence of infused CAR-T cells and chromosomal abnormalities due to genome editing, remain to be addressed. Thus, recent clinical trials on universal CAR-T cells are summarized and future perspectives to overcome current challenges are discussed in this review.