CAR-T Cell Therapy: From the Shop to Cancer Therapy

Abstract

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

PRMT1 in human neoplasm: cancer biology and potential therapeutic target

“…Therefore, it is crucial to explore more selective PRMT1-targeted inhibitors that have fewer side effects and improved efficacy. Furthermore, it is equally important to consider new therapeutic avenues of research, such as prime editing [ 148 ], proteolysis targeting chimera (PROTAC) [ 149 ], and CAR-T cell therapy [ 150 ].…”

Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin’s Lymphoma

“…Fundamental immunological discoveries around the 1800s contributed to broadening the understanding of T cells and their potential clinical utilization to treat disease (Figure 1). Between the 1980s and 1990s, Dr. Zelig Eshhar from the Weizmann Institute of Science pioneered the novel concept of chimeric antigen receptors [16,17] that ultimately led to the design of the current CAR utilized therapeutically [18][19][20][21].…”

“…1990s -June and Sadelain were able to optimally expand the genetically engineered T cells and infuse them into patients [43][44][45][46][47][48][49]. 1998 -Development of 2 nd generation of CAR-T cells with CD28 co-stimulatory domain [18,50]. 2003 -Development of CD19directed CARs [51].…”

“…2011 -Development of 4 th generation CARs also known as TRUCKs [58]. 2017 -FDA approval of CD19 CAR-T cell therapies Yescarta (axicabtagene cilloleucel) and Kymriah (tisagenlecleuccel) for refractory or relapsed leukemia and lymphoma patients [18,59,60]. 2020-2022 -Various other CAR-T cell therapies have been approved by the FDA over years: Tecartus (Brexucabtagene autoleucel), Breyanzi (Lisocabtagene maraleucel), Abecma (Idecabtagene vicleucel), Carvykti (Ciltacabtagene autoleucel) [18,19,[61][62][63][64].…”

“…2017 -FDA approval of CD19 CAR-T cell therapies Yescarta (axicabtagene cilloleucel) and Kymriah (tisagenlecleuccel) for refractory or relapsed leukemia and lymphoma patients [18,59,60]. 2020-2022 -Various other CAR-T cell therapies have been approved by the FDA over years: Tecartus (Brexucabtagene autoleucel), Breyanzi (Lisocabtagene maraleucel), Abecma (Idecabtagene vicleucel), Carvykti (Ciltacabtagene autoleucel) [18,19,[61][62][63][64]. Created in BioRender.com CAR DOMAIN-STRUCTURE FUNCTION CAR-T cells usually consist of a target antigen-binding domain, hinge sequence motif, a transmembrane domain, and one or more intracellular signaling domains [30,31].…”