CRISPR-engineered T cells in patients with refractory cancer

@article{Stadtmauer2020CRISPRengineeredTC,
  title={CRISPR-engineered T cells in patients with refractory cancer},
  author={Edward A Stadtmauer and Joseph A. Fraietta and Megan M. Davis and Adam D. Cohen and Kristy Weber and Eric Lancaster and Patricia A. Mangan and Irina Kulikovskaya and Minnal Gupta and Fang Chen and Lifeng Tian and Vanessa E. Gonzalez and Jun Xu and In-Young Jung and J. Joseph Melenhorst and Gabriela Plesa and Joanne Shea and Tina Matlawski and Amanda Cervini and Avery L Gaymon and Stephanie Desjardins and Anne Lamontagne and January Salas-Mckee and Andrew D. Fesnak and Donald L Siegel and Bruce L. Levine and Julie K. Jadlowsky and Regina M Young and Anne Chew and Wei-Ting Hwang and Elizabeth O. Hexner and Beatriz M Carreno and Christopher L. Nobles and Frederic D. Bushman and Kevin R. Parker and Yanyan Qi and A. Satpathy and Howard Y. Chang and Yangbing Zhao and Simon F. Lacey and Carl H. June},
  journal={Science},
  year={2020},
  volume={367}
}
CRISPR takes first steps in humans CRISPR-Cas9 is a revolutionary gene-editing technology that offers the potential to treat diseases such as cancer, but the effects of CRISPR in patients are currently unknown. Stadtmauer et al. report a phase 1 clinical trial to assess the safety and feasibility of CRISPR-Cas9 gene editing in three patients with advanced cancer (see the Perspective by Hamilton and Doudna). They removed immune cells called T lymphocytes from patients and used CRISPR-Cas9 to… 
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CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases.
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This comprehensive review paper discusses the origin of CRISPR-Cas9 systems and their therapeutic potential against various genetic disorders, including cancer, allergy, immunological disorders, Duchenne muscular dystrophy, cardiovascular disorders, neurological disorders, liver-related disorders, cystic fibrosis, blood- related disorders, eye-related Disorders, and viral infection.
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Delivery of CRISPR/Cas systems by physical methods, viral vectors and non-viral vectors for cancer gene therapy and immunotherapy and promising advances in cancer treatment using CRISpr/ Cas systems are discussed.
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References

SHOWING 1-10 OF 62 REFERENCES
Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9.
TLDR
It is demonstrated that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy.
Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes
TLDR
It is demonstrated that Cas9 protein can be modified to eliminate immunodominant epitopes through targeted mutation while preserving its function and specificity and highlights the problem of pre-existing immunity against CRISPR-associated nucleases and offers a potential solution to mitigate the T cell immune response.
CRISPR–Cas9 genome engineering of primary CD4+ T cells for the interrogation of HIV–host factor interactions
TLDR
This protocol describes how to design, synthesize, and deliver CRISPR–Cas9 RNPs to primary CD4+ T cells for targeted gene knockout, and shows how the edited cells can be used for the analysis of host factors in HIV replication.
CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients
TLDR
For the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1 is described, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.
Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition
TLDR
Gene-disrupted allogeneic CAR and TCR T cells could provide an alternative as a universal donor to autologous T cells, which carry difficulties and high production costs.
Prevalence of Pre-existing Antibodies to CRISPR-Associated Nuclease Cas9 in the USA Population
TLDR
ELISA-based assays that are capable of detecting antibodies to Cas9 from Staphylococcus aureus and Streptococcs pyogenes in human sera are described and the prevalence of anti-SaCas9 and anti-SpCas9 antibodies is found to be 10% and 2.5%, respectively.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
TLDR
Improved therapeutic efficacy of Cas9-edited CAR T cells is demonstrated and the potential of precision genome engineering to enhance next-generation cell therapies is highlighted.
Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6
TLDR
This work describes a method to multiplex homologous recombination in human hematopoietic stem and progenitor cells and primary human T cells by combining rAAV6 donor delivery and the CRISPR/Cas9 system delivered as ribonucleoproteins (RNPs).
A versatile system for rapid multiplex genome-edited CAR T cell generation
TLDR
This study accomplished rapid and efficient multiplex genomic editing, and re-directing T cells with antigen specific CAR via a one-shot CRISPR protocol by incorporation of multiple gRNAs in a CAR lentiviral vector.
In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system
TLDR
An efficient method to induce specific chromosomal rearrangements in vivo using viral-mediated delivery of the CRISPR/Cas9 system to somatic cells of adult animals is described, substantially expands the ability to model human cancers in mice and potentially in other organisms.
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