Special issue: CAR-T cell therapy for hematological malignancies

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell derived hematological malignancies, including acute lymphoblastic leukemia (ALL), B-cell non-Hodgkin lymphoma (B-NHL), and multiple myeloma (MM). CD19-targeted CAR-T cells yield complete remission (CR) rates of about 90% in R/R ALL and about 50% in R/R NHL, respectively, while BCMA-targeted CAR-T cells yield CR rate of about 50%−80% in R/R MM. Notably, the US Food and Drug Administration have approved six CAR-T cell products (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel) for the treatment of R/R B-NHL, R/R ALL, and R/R MM. However, some patients might not respond to such therapy or quickly relapse after CAR-T cell infusion, which is likely due to the dysfunction and poor persistence of CAR-T cells or the modulation of specific antigen. Thus, alternative treatment strategies must be investigated. In addition, accumulating research have been conducted to discover novel target of antigens with therapeutic efficacy and utility for generating CAR-T cells against acute myeloid leukemia (AML). Safety during CAR-T cell treatment is another important issue, concerning complications such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), pancytopenia, and infection. Despite the fact that the majority of those adverse effects are minimal, the risk of a life-threatening situation still exists. Cautious treatment for severe adverse events requires a multidisciplinary approach with involvement of not only oncologists but also other internal medicine doctors to guarantee diagnosis and treatment in time. Therefore, it is of vital importance to understand the novel advances of CAR-T cell therapy.

This special issue of ImmunoMedicine focuses on novel developments of CAR-T cell therapy for hematological malignancies. The review from Xiangmin Wang (https://doi.org/10.1002/imed.1030) summarized the non-BCMA targeted CAR-T cell therapies for MM. Novel targets including CS1, CD38, CD138, NKG2D, CD70, TACI, and etc. might have the potential to prevent the recurrence and enhance treatment efficiency. The review from Elaine Tan Su Yin (https://doi.org/10.1002/imed.1039) summarized the current breakthrough and future perspectives of CD20-targeted CAR-T cell therapy for hematologic malignancies, especially for R/R B-NHL. The review from Yue Huang (https://doi.org/10.1002/imed.1031) summarized the current achievement and potential AML-associated cell markers of CAR-T cell therapy in AML preclinical studies and clinical trials, and discusses the future directions of CAR-T cell therapy in patients with AML. The review from Yuanyuan Hao (https://doi.org/10.1002/imed.1029) summarized the effects of tumor-derived exosomes (TEXs) on the survival and functions of T cell subsets, as well as their clinical applications.

This special issue also contains three original research articles reporting clinical trials of CAR-T cell therapy. Linghui Zhou et al. (https://doi.org/10.1002/imed.1036) reported the data of infections post CAR-T cell therapy, and found that it was a common complication in patients with hematological malignancies treated by CD19 CAR-T cells, which means clinicians should pay more attention to such situations. Kaiting Tang et al. (https://doi.org/10.1002/imed.1037) presented three cases of compassionate CAR-T cell therapy in advanced B-ALL, and shared their experiences on treating patients with high disease burden. Yue Huang et al. (https://doi.org/10.1002/imed.1032) reported an R/R ALL patient with high leukemia burden and central nervous system involvement, who responded to donor-derived HLA-matched allogeneic CAR-T treatment and achieved quick CR.

We thank all the authors for their insightful contributions. This special issue provides an overview of the current knowledge regarding the most recent advances of CAR-T cell therapy, including CAR-T cell function, diverse applications, and complications with coping strategies. We hope that this issue will appeal to researchers as they explore fundamental and clinical aspects of CAR-T cell therapy.