Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy

Naeem, Muhammad Asif; Hazafa, Abu; Bano, Naheed; Rashid, Asif; Farooq, Muhammad; Razak, Saiful Izwan Abd; Lee, Tze Yan; Devaraj, Sutha

doi:10.1016/j.lfs.2023.121409

Cited by 12 publications

(12 citation statements)

References 106 publications

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“…Another aspect of cellular immunotherapy rapidly developing in parallel with advanced CAR technologies aims to produce superior and more affordable allogeneic "off-the-shelf " therapeutic cells enhanced by gene editing technologies [192][193][194][195][196]. The combination of various gene engineering techniques can modulate T cell activation and proliferation and have resistance to inhibitory signals from the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

et al. 2023

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Cancer immunotherapies utilizing genetically engineered T cells have emerged as powerful personalized therapeutic agents showing dramatic preclinical and clinical results, particularly in hematological malignancies. Ectopically expressed chimeric antigen receptors (CARs) reprogram immune cells to target and eliminate cancer. However, CAR T cell therapy's success depends on the balance between effective anti-tumor activity and minimizing harmful side effects. To improve CAR T cell therapy outcomes and mitigate associated toxicities, scientists from different fields are cooperating in developing next-generation products using the latest molecular cell biology and synthetic biology tools and technologies. The immunotherapy field is rapidly evolving, with new approaches and strategies being reported at a fast pace. This comprehensive literature review aims to provide an up-to-date overview of the latest developments in controlling CAR T cell activity for improved safety, efficacy, and flexibility.

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Section: Discussionmentioning

confidence: 99%

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

et al. 2023

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“…CRISPR/Cas9 genome editing provides a unique platform to modify CAR T cells to overcome some of these deficiencies. [46][47][48] However, the current platform of utilizing electroporation to deliver CRISPR/Cas9 editing molecules can be detrimental to T-cell fitness resulting in poor viability and expansion, in additional to causing possible chromosomal breakage. 49,50 Hence, alternative methods to deliver CRISPR/Cas9 editing molecules need to be explored.…”

Section: Discussionmentioning

confidence: 99%

Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow

Yu,

Jhita,

Shankles

et al. 2023

Lab Chip

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“…The CRISPR/Cas9 genome editing technology, used to knock-out TCR alpha constant (TRAC) and HLA genes, appears to be a safe and promising method for CAR-T cells modification. 52 Phase 1 study presented by Ottaviano et al 53 showed the utility of CRISPR/Cas9 editing to disrupt the TCR α chain and remove CD52, which resulted in allo TT52CAR19 T cells. In four of the six pediatric patients with B-ALL, the administered cells demonstrated activity and expansion.…”

Section: Major Challengesmentioning

confidence: 99%

“…Strategies to overcome GvHD and alloimmunity [51][52][53][54][55][56][57][58][59][60][61][62]. CAR, chimeric antigen receptor; HLA, human leukocyte antigens; TCR, T-cell receptor.…”

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confidence: 99%

Are we ready for personalized CAR‐T therapy?

Strzelec

Helbig

2023

European J of Haematology

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The future of chimeric antigen receptor T (CAR‐T) therapy remains unclear. New studies are constantly being published confirming the efficacy and favorable safety profile of its innovative enhancements. Currently approved CAR‐T drugs are manufactured exclusively for a specific patient from the recipient's own cells. This does not close the door to further modifications with subsequent personalization and better adaptation to the individual needs. Bringing such a drug to market would involve raising the already high costs, so it is necessary to lower the existing ones. On the other hand, so‐called universal CAR‐T are also getting closer to the patient's bed, but its implementation may struggle with multiple challenges, including development of graft‐versus‐host disease (GvHD) and alloimmunity. However, that off‐the‐shelf therapy could prove useful as a quick solution for patients in very poor condition or excluded from current therapy due to manufacturing limitations. The introduction of currently tested solutions may undoubtedly change the current paradigm of treatment.

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Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy

Cited by 12 publications

References 106 publications

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow

Are we ready for personalized CAR‐T therapy?

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