Advances in CAR-T Cell Therapy

Dear Colleagues,

In recent decades, we have witnessed the potential of targeting the immune system and the clinical impact of modulating immune response in the treatment of cancer. Research on immune checkpoints such as PD-1 and CTLA-4 has laid this foundation, with multiple approvals of anti-PD-1 and anti-CTLA-4 blockers as monotherapy and combination therapy for the treatment of cancer. The need for further improvement in response and survival rates has led to the development of cell therapies such as tumor-specific chimeric antigen receptor (CAR-) T cell therapy, NK cell therapy, and γδ-T-cell therapy. Among the different cell therapies, CAR-T cell therapy has seen significant success as the structure of CAR evolved from the first generation that had no intracellular signaling domain to CARs with one or two intracellular signaling domains with or without the ability to secrete cytokines or blocking proteins. Impressive clinical outcomes such as objective response rates (ORRs) as high as 100% in certain hematological cancers and responses durable over 10 years in some patients were seen with CAR-T cell therapy. To date, six CAR-T cell therapies, including axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), tisagenlecleucel (Kymriah), lisocabtagene maraleucel (Breyanzi), idecabtagene vicleucel (Abecma), and ciltacabtagene autoleucel (Carvykti), have been approved by the US FDA for different hematological cancers.

However, CAR-T cells are limited by several challenges like low responses in solid tumors, the development of resistance due to antigen loss, exhaustion of CAR-T cells due to tonic signaling, waiting time for the manufacture of CAR-T cells, and manufacturing inconsistencies and failures. Preclinical, translational, and clinical research aiming to improve the durability of responses, extending the success to solid tumors, and addressing concerns related to time to manufacture cell therapy is currently underway.

This Special Issue aims to broadly attract research focused on CAR-T cell therapy. Clinical prospective, retrospective, and observational real-world studies and preclinical and translational studies are welcome to be submitted. Case reports may be considered on a case-by-case basis if they include the detailed elucidation of molecular mechanisms or comprehensive literature-based discussions. While we expect to receive articles related to cancer treatment, non-oncology applications of CAR-T cells such as autoimmune disorders are also considered to be within the scope of this Special Issue.

Dr. Anand Rotte
Guest Editor

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• chimeric antigen receptors
• CAR-T cells
• binding domains
• T cells redirected for universal cytokine-mediated killing (TRUCKs)
• response
• CRS
• ICANS
• safety
• cancer
• solid tumors
• hematological malignancies and autoimmune disorders