Safety Strategies of Genetically Engineered T Cells in Cancer Immunotherapy

Ren, Yanru; Sun, Shangjun; Han, Sun‐Young

doi:10.2174/1381612824666171227222624

Cited by 7 publications

(13 citation statements)

References 61 publications

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“…Researchers have been developing some safety strategies to prevent or reduce the adverse effects of CAR-T cell therapies. The T cells so manufactured are called next-generation CAR-T cells [ 9 , 28 , 31 , 40 ].…”

Section: Reviewmentioning

confidence: 99%

“…Suicide gene switch: It includes expressing a specific gene into the CAR T cells, which acts as a 'safety suicide gene switch' (activated by administering non-toxic molecules or associated monoclonal antibodies) to destroy the CAR T cells whenever there is a development of severe toxicity [ 9 , 31 ].…”

Section: Reviewmentioning

confidence: 99%

“…The engineered CAR-T cell demonstrates a significant cell lysis activity after the use of the molecule inducer in a dose-dependent manner. The development of these novel controlled CAR-T cells opens innovative and attractive ways to control potentially adverse effects by improving the safety of CAR-T cell therapy in the clinic [ 9 , 28 ].…”

Section: Reviewmentioning

confidence: 99%

“…Combinatorial target-antigen recognition: It involves engineering the T Cells with two different CARs, which may be fully activated only after recognizing a set of different antigens expressed simultaneously on the tumor cells; e.g., the combination of CAR + Chimeric costimulatory receptor, Bispecific Tandem CAR. The normal cells that express only one of these antigens cant activate these T cells, thus significantly reducing on-target/off-tumor toxicity [ 9 , 28 ].…”

Section: Reviewmentioning

confidence: 99%

“…As compared to stem cell transplants, which also involve aggressive chemotherapy, most patients have a rapid recovery with CAR-T cell therapy [ 8 ]. Unlike TILs and TCRs, which are dependent on Major histocompatibility complex (MHC) expression of target cells for antigen recognition, CAR-T cells recognize the specific antigens, independent of antigen processing by the target cells and MHC restrictions, thus, in turn, killing tumor cells effectively [ 3 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead

Reddy¹,

Llukmani²,

Hashim³

et al. 2021

Cureus

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Immunotherapy is the upcoming trend in cancer treatment. Traditional cancer treatment methods include surgical resection, radiotherapy, chemotherapy, small molecule targeted drugs, monoclonal antibodies, and hematopoietic stem cell transplantation (HSCT). Surgical resection is useful for early-stage patients but not for metastatic cancer cells; radiotherapy and chemotherapy are more common but produce substantial damage to normal tissues and have poor selectivity. Targeted drugs, including monoclonal antibodies, have better comprehensive efficacy but can also encourage gene mutation of tumor cells and drug tolerance. HSCT is effective, but choosing a donor is often difficult, and the graft is also prone to rejection. Thus, chimeric antigen receptor (CAR)-T cell therapy, a form of cellular/adoptive immunotherapy, is at the forefront of cancer therapy treatments due to its sustained remission, fewer side effects, and a better quality of life. CAR-T cell therapy involves genetically modifying the T cells and multiplying their numbers to kill cancer cells. This review article gives an insight into how the CAR-T cells have evolved from simple T cells with modest immune function to genetically engineered robust counterparts that brought great hope in the treatment of hematological malignancies. Much research has been undertaken during the past decade to design and deliver CAR-T cells. This has led to successful outcomes in leukemias, lymphomas, and multiple myeloma, paving the way for expanding CAR therapy. Despite tremendous progress, CAR-T cell therapies are faced with many challenges. Areas for improvement include limited T cell persistence, tumor escape, immunosuppressive components in the tumor microenvironment, cancer relapse rate, manufacturing time, and production cost. In this manuscript, we summarize the innovations in the design and delivery of CAR technologies, their applications in hematological malignancies, limitations to its widespread application, latest developments, and the future scope of research to counter the challenges and improve its effectiveness and persistence.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%