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Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development. Significance statement: The necessity and importance of chimeric antigen receptor (CAR) T cells and their therapeutic efficiency in treating diseases other than cancer, mainly cardiovascular diseases, have emerged in recent years. However, there is still room for advancement in the current models of CAR‐T cell therapy. This paper highlights the evolution and roadblocks of CAR‐T technology at different levels, from technical concerns to clinical outcomes, in an attempt to improve the therapeutic efficiency of CAR‐T cell therapy in this area. [ABSTRACT FROM AUTHOR]

• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]

As genetically engineered cells, chimeric antigen receptor (CAR)-T cells express specific receptors on their surface to target and eliminate malignant cells. CAR proteins are equipped with elements that enhance the activity and survival of T cells. Once injected, CAR-T cells act as a "living drug" against tumor cells in the body. Up to now, CAR-T cell therapy has been demonstrated as a robust adoptive cell transfer (ACT) immunotherapeutic modality for eliminating tumor cells in refractory hematological malignancies. CAR-T cell therapy modality involves several steps, including the collecting of the blood from patients, the isolation of peripheral blood mononuclear cells (PBMCs), the enrichment of CD4+/CD8+ T cell, the genetic reprogramming, the expansion of modified T cells, and the injection of genetically engineered T cells. The production of CAR-T cells is a multi-step procedure, which needs precise and safety management systems, including good manufacturing practice (GMP), and in-line quality control and assurance. The current study describes the structure of CARs and concentrates on the next generations of CARs that are engaged in enhancing the anti-tumor responses and safety of the engineered T cells. This paper also highlights the important concerns in quality control and nonclinical research of CAR-T cells, as well as general insights into the manufacture, reprogramming, and application of CAR-T cells based on new and enhanced techniques for treating hematological malignancies. Besides, the application of the CRISPR-Cas9 genome editing technology and nanocarrier-based delivery systems containing CAR coding sequences to overcome the limitations of CAR-T cell therapy has also been explained. [Display omitted] [ABSTRACT FROM AUTHOR]