Abstract
Purpose: The aim is to review the current advances in designing safer and more efficient CAR-T cells and discuss the future research possibilities for the treatment of both hematological malignancies and solid tumors. Study Design: An extensive review was carried out on the basic structure of CARS, current advances to design safer and more efficient CAR-T cells, and future research possibilities for the treatment of both hematological malignancies and solid tumors. Results: Encouragement of chimeric antigen receptor-T (CAR-T) cell therapy as one of adoptive immunotherapy is increasingly important in recent years. Its preparation is based on the genetic modification of individual T cells. The innovation of the functional intracellular signaling domain is a critical part of the genetically modified T cells and requires a long journey of development that has resulted in several improvements in the safety and effectiveness of CAR-T cells. CAR-T cell therapy can be modified rapidly and has great and strong application potential according to a large number of global clinical trials. This article briefly describes the basic structure and design of CARs and discusses current trends in the development of safer and more efficient CAR-T cells for the treatment of both hematological and solid malignancies and looks forward to future research possibilities. Conclusion: It is concluded that conclude that the prospect of this technology lies in CAR-T cell engineering which can overcome aggressive TMEs and recruiting an endogenous tumor response. The final task for researchers in this field is to carry out clinical trials and secure the funding needed to complete their clinical trials. This immunotherapy continues to progress and more records of successful malignancy eradication occur.
Highlights
The growing incidence of malignant tumorhas increased worldwide that threatens individual healthand society in both respects
chimeric antigen receptor-T (CAR-T) cells expressing the macrophage colony-stimulating factor 1 receptor (CSF-1R) were receptive to CSF-1, which reinforced the proliferative effects of chimeric antigen receptors (CARs) signaling without sacrificing cytotoxicity and did not provoke trans-differentiation into the myeloid lineage
Due to its effect on fibroblast activation protein (FAP)+stromal cells in the bone marrow, FAP targeted CAR-T cells led to cachexia and bone toxicity while having restricted effect on the maturation of various tumors in immuno-competent mice (Tran et al, 2013). In another immuno-competent mice trial, FAP targeted CAR-T cells with a specific anti-FAP scFv reduced tumor growth when used in Overcoming direct T cell inhibitory signals: Resolving the direct inhibitory signals from T cells present in the tumor microenvironment (TME) is an important issue for CAR T cells
Summary
The growing incidence of malignant tumorhas increased worldwide that threatens individual healthand society in both respects. Avidin-linked CARs, which in combination with biotinylated antibodies often called biotin-binding immune receptors, may be used to regulate CAR-T cell activity similar to a safety switch and to target different antigens, whether sequentially, or at the same time (Lohmuelleret al., 2017).
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