The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition
Open accessPublished version of a preprint
Abstract
Purpose: Using gene-disrupted allogeneic T cells as universal effector cells provides an alternative and potentially improves current chimeric antigen receptor (CAR) T-cell therapy against cancers and infectious diseases. Experimental Design: The CRISPR/Cas9 system has recently emerged as a simple and efficient way for multiplex genome engineering. By combining lentiviral delivery of CAR and electro-transfer of Cas9 mRNA and gRNAs targeting endogenous TCR, β-2 microglobulin (B2M) and PD1 simultaneously, to generate gene-disrupted allogeneic CAR T cells deficient of TCR, HLA class I molecule and PD1. Results: The CRISPR gene–edited CAR T cells showed potent antitumor activities, both in vitro and in animal models and were as potent as non-gene–edited CAR T cells. In addition, the TCR and HLA class I double deficient T cells had reduced alloreactivity and did not cause graft-versus-host disease. Finally, simultaneous triple genome editing by adding the disruption of PD1 led to enhanced in vivo antitumor activity of the gene-disrupted CAR T cells. Conclusions: 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. Gene-disrupted CAR and TCR T cells with disabled checkpoint molecules may be potent effector cells against cancers and infectious diseases. Clin Cancer Res; 23(9); 2255–66. ©2016 AACR.
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“CRISPR-Cas9 genetic ablation of checkpoint targets such as PD-1 in adoptive T cell therapies has also shown increased functionality in certain models and is being persued clinically (Ren et al., 2017; Rupp et al., 2017; Stadtmauer et al., 2020; Su et al., 2016).”
From Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies (2020) · cites this paper as Ren et al., 2017
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Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
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Self-citationChimeric antigen receptor–modified T cells in chronic lymphoid leukemia
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Self-citationChimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
Self-citationHigh-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673
Rationally engineered Cas9 nucleases with improved specificity
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Easy quantitative assessment of genome editing by sequence trace decomposition
Brinkman, E. K., Chen, T., Amendola, M., & van Steensel, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku936 · Cited by 2,390
Brentjens, R. J., Davila, M. L., Riviere, I., Park, J., Wang, X., Cowell, L. G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005930 · Cited by 2,063
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Self-citationCRISPR-engineered T cells in patients with refractory cancer
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Metadata
- Authors
- Ren, J., Liu, X., Fang, C., Jiang, S., June, C. H., & Zhao, Y.
- Affiliations
- Abramson Cancer Center (US)
- Corresponding author
- June, Carl H.
- Zhao, Yangbing
- Venue
- Clinical Cancer Research
- Published
- 2017-04-30
- Volume
- 23
- Issue
- 9
- Pages
- 2255-2266
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC5413401
- OpenAlex
- W2548694234
- Cited by
- 942
- References
- 42
- Citations by year
- 2026: 58 · 2025: 87 · 2024: 104 · 2023: 98 · 2022: 104 · 2021: 125 · 2020: 116 · 2019: 113 · 2018: 74 · 2017: 59
- FWCI
- 44.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA120409, P30CA016520)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- universal CAR-T cells, allogeneic CAR T cells, multiplex genome editing, CRISPR/Cas9, anti-PD-1 resistance, HLA class I deficiency, beta2-microglobulin, lentiviral gene delivery, graft-versus-host disease, alloreactivity, anticancer activity, immune checkpoint blockade
- MeSH terms
- Gene Editing, Graft vs Host Disease, Humans, Lymphocyte Activation, Neoplasms, Receptors, Antigen, T-Cell, T-Lymphocytes, Immunotherapy, Adoptive, Severe Combined Immunodeficiency, Programmed Cell Death 1 Receptor, CRISPR-Cas Systems
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