CRISPR/Cas systems to overcome challenges in developing the next generation of T cells for cancer therapy

Huang, Dennis; Miller, Matthew S.; Ashok, Bhaargavi; Jain, Samagra; Peppas, Nicholas A.

doi:10.1016/j.addr.2020.07.015

Cited by 15 publications

(14 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cardiovascular medicine, CRISPRbased tools have multiple applications, with a primary focus on direct therapeutic interventions to treat inherited cardiac disorders (Vermersch et al, 2020). CRISPR also represents a breakthrough advance in genetically engineered immune cells (Huang et al, 2020), personalized cancer medicine (Li and Kasinski, 2020), and modification of human embryos (Tang et al, 2017). Even in the current novel coronavirus (COVID-19) outbreak, CRISPR-based technology has shown strong application value.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Feng

Wang

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems have revolutionized traditional gene-editing tools and are a significant tool for ameliorating gene defects. Characterized by high target specificity, extraordinary efficiency, and cost-effectiveness, CRISPR/Cas systems have displayed tremendous potential for genetic manipulation in almost any organism and cell type. Despite their numerous advantages, however, CRISPR/Cas systems have some inherent limitations, such as off-target effects, unsatisfactory efficiency of delivery, and unwanted adverse effects, thereby resulting in a desire to explore approaches to address these issues. Strategies for improving the efficiency of CRISPR/Cas-induced mutations, such as reducing off-target effects, improving the design and modification of sgRNA, optimizing the editing time and the temperature, choice of delivery system, and enrichment of sgRNA, are comprehensively described in this review. Additionally, several newly emerging approaches, including the use of Cas variants, anti-CRISPR proteins, and mutant enrichment, are discussed in detail. Furthermore, the authors provide a deep analysis of the current challenges in the utilization of CRISPR/Cas systems and the future applications of CRISPR/Cas systems in various scenarios. This review not only serves as a reference for improving the maturity of CRISPR/Cas systems but also supplies practical guidance for expanding the applicability of this technology.

show abstract

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Feng

Wang

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…A growing number of preclinical studies based on rodent and other animal models indicate that CRISPR-Cas systems have the potential for therapeutic usage in different diseases, including genetic diseases, 31 infectious diseases, 32 cancers, 7 , 33 immunological diseases (autoimmunity and immunodeficiency), 34 etc.…”

Section: Preclinical Testsmentioning

confidence: 99%

Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics

Liu

Jiang

et al. 2021

Precision Clinical Medicine

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats-CRISPR associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the fast progress in basic researches and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing tool-kits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.

show abstract

“…TCR-based ACT overcomes the first of these barriers by the ex vivo manufacture of up to billions of activated lymphocytes with known selectivity and potency. The majority of TCR structures are heterodimers comprised of α- and β-chains that are covalently linked via a disulfide bond between the conserved cysteine residues located within the constant region of each chain [ 3 ]. Neither TCR chain has intrinsic signaling capacity, and activation requires interaction between the TCR and other accessory signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

“…Neither TCR chain has intrinsic signaling capacity, and activation requires interaction between the TCR and other accessory signaling molecules. A non‐covalent oligomeric complex comprised of TCR and CD3 signaling molecules (CD3ζ, CD3δε, and CD3γε) initiates signaling activity on binding a cognate peptide MHC complex on the target cell and enables antigen-specific tumor cell lysis [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

Tsimberidou

Morris

et al. 2021

J Hematol Oncol

View full text Add to dashboard Cite

T-cell receptor (TCR)-based adoptive therapy employs genetically modified lymphocytes that are directed against specific tumor markers. This therapeutic modality requires a structured and integrated process that involves patient screening (e.g., for HLA-A*02:01 and specific tumor targets), leukapheresis, generation of transduced TCR product, lymphodepletion, and infusion of the TCR-based adoptive therapy. In this review, we summarize the current technology and early clinical development of TCR-based therapy in patients with solid tumors. The challenges of TCR-based therapy include those associated with TCR product manufacturing, patient selection, and preparation with lymphodepletion. Overcoming these challenges, and those posed by the immunosuppressive microenvironment, as well as developing next-generation strategies is essential to improving the efficacy and safety of TCR-based therapies. Optimization of technology to generate TCR product, treatment administration, and patient monitoring for adverse events is needed. The implementation of novel TCR strategies will require expansion of the TCR approach to patients with HLA haplotypes beyond HLA-A*02:01 and the discovery of novel tumor markers that are expressed in more patients and tumor types. Ongoing clinical trials will determine the ultimate role of TCR-based therapy in patients with solid tumors.

show abstract

CRISPR/Cas systems to overcome challenges in developing the next generation of T cells for cancer therapy

Cited by 15 publications

References 135 publications

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics

T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

Contact Info

Product

Resources

About