Current status and hurdles for CAR-T cell immune therapy.

Chimeric antigen receptor T (CAR-T) cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies. There are several key components critical for development and application of CAR-T therapy. First, the design of CAR vectors can considerably affect several aspects of the physiological functions of these T cells. Moreover, despite the wide use of γ-retrovirus and lentivirus in mediating gene transfer into T cells, optimal CAR delivery systems are also being developed and evaluated. In addition, several classes of mouse models have been used to evaluate the efficacies of CAR-T cells; however, each model has its own limitations. Clinically, although surprising complete remission (CR) rates were observed in acute lymphoblastic leukemia (ALL), lymphoma, and multiple myeloma (MM), there is still a lack of specific targets for acute myeloid leukemia (AML). Leukemia relapse remains a major challenge, and its mechanism is presently under investigation. Cytokine release syndrome (CRS) and neurotoxicity are life-threatening adverse effects that need to be carefully treated. Several factors that compromise the activities of anti-solid cancer CAR-T cells have been recognized, and further improvements targeting these factors are the focus of the development of novel CAR-T cells. Overcoming the current hurdles will lead to optimal responses of CAR-T cells, thus paving the way for their wide clinical application.