Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

Nature

Volumn 543, Issue 7643, 2017, Pages 113-117

  Eyquem, Justin ^a   Mansilla Soto, Jorge ^a   Giavridis, Theodoros ^a   Van Der Stegen, Sjoukje J C ^a   Hamieh, Mohamad ^a   Cunanan, Kristen M ^a   Odak, Ashlesha ^a   Gönen, Mithat ^a   Sadelain, Michel ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAS9 PROTEIN; CD19 ANTIGEN; CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN; CHIMERIC ANTIGEN RECEPTOR; CRISPR ASSOCIATED PROTEIN; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; UNCLASSIFIED DRUG; LYMPHOCYTE ANTIGEN RECEPTOR;

ANTIGEN; CELLS AND CELL COMPONENTS; DISEASE TREATMENT; GENE; GENE EXPRESSION; GENETIC ENGINEERING; GENOME; TUMOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL CELL; ANIMAL MODEL; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; CRISPR CAS SYSTEM; EXHAUSTION; GENE EDITING; GENE EXPRESSION; GENE LOCUS; GENE TARGETING; HUMAN; HUMAN CELL; IMMUNOBIOLOGY; IN VITRO STUDY; IN VIVO STUDY; INTERNALIZATION; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TUMOR REJECTION; TUMOR XENOGRAFT; ANIMAL; CELL DIFFERENTIATION; CYTOLOGY; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; MALE; METABOLISM; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROCEDURES; PROMOTER REGION; TRANSLATIONAL RESEARCH;

ANIMALS; ANTIGENS, CD19; CELL DIFFERENTIATION; CRISPR-CAS SYSTEMS; DISEASE MODELS, ANIMAL; GENE EDITING; GENE EXPRESSION REGULATION; GENETIC LOCI; HUMANS; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; MALE; MICE; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROMOTER REGIONS, GENETIC; RECEPTORS, ANTIGEN, T-CELL; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; T-LYMPHOCYTES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 85014564234     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature21405     Document Type: Article

References (34)

1. Jensen, M. C. & Riddell, S. R. Designing chimeric antigen receptors to effectively and safely target tumors. Curr. Opin. Immunol. 33, 9-15 (2015).
2. Brentjens, R. J. et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat. Med. 9, 279-286 (2003).
3. Sadelain, M. CAR therapy: the CD19 paradigm. J. Clin. Invest. 125, 3392-3400 (2015).
4. Sadelain, M. & Mulligan, R. C. Efficient retroviral-mediated gene transfer into murine primary lymphocytes. Ninth International Immunology Congress, Budapest. 88:34. (1992).
5. Wang, X. & Rivière, I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol. Ther. Oncolytics. 3, 16015 (2016).
6. Ellis, J. Silencing and variegation of gammaretrovirus and lentivirus vectors. Hum. Gene Ther. 16, 1241-1246 (2005).
7. Rivière, I., Dunbar, C. E. & Sadelain, M. Hematopoietic stem cell engineering at a crossroads. Blood 119, 1107-1116 (2012).
8. von Kalle, C., Deichmann, A. & Schmidt, M. Vector integration and tumorigenesis. Hum. Gene Ther. 25, 475-481 (2014).
9. Wright, A. V., Nuñez, J. K. & Doudna, J. A. Biology and applications of CRISPR systems: harnessing nature's toolbox for genome engineering. Cell 164, 29-44 (2016).
10. Tsai, S. Q. & Joung, J. K. Defining and improving the genome-wide specificities of CRISPR-Cas9 nucleases. Nat. Rev. Genet. 17, 300-312 (2016).
11. Lombardo, A. et al. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat. Methods 8, 861-869 (2011).
12. Sather, B. D. et al. Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template. Sci. Transl. Med. 7, 307ra156 (2015).
13. Brentjens, R. J. et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5, 177ra38 (2013).
14. Wang, J. et al. Highly efficient homology-driven genome editing in human T cells by combining zinc-finger nuclease mRNA and AAV6 donor delivery. Nucleic Acids Res. 44, e30 (2016).
15. Hubbard, N. et al. Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome. Blood 127, 2513-2522 (2016).
16. Corthay, A., Nandakumar, K. S. & Holmdahl, R. Evaluation of the percentage of peripheral T cells with two different T cell receptor alpha-chains and of their potential role in autoimmunity. J. Autoimmun. 16, 423-429 (2001).
17. de Vree, P. J. et al. Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. Nat. Biotechnol. 32, 1019-1025 (2014).
18. Zhao, Z. et al. Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell 28, 415-428 (2015).
19. Blackburn, S. D. et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10, 29-37 (2009).
20. Gattinoni, L. et al. A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290-1297 (2011).
21. Gallardo, H. F., Tan, C. & Sadelain, M. The internal ribosomal entry site of the encephalomyocarditis virus enables reliable coexpression of two transgenes in human primary T lymphocytes. Gene Ther. 4, 1115-1119 (1997).
22. Long, A. H. et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat. Med. 21, 581-590 (2015).
23. Sommermeyer, D. et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia 30, 492-500 (2016).
24. Frigault, M. J. et al. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells. Cancer Immunol. Res. 3, 356-367 (2015).
25. Schrum, A. G., Turka, L. A. & Palmer, E. Surface T-cell antigen receptor expression and availability for long-term antigenic signaling. Immunol. Rev. 196, 7-24 (2003).
26. Liu, H., Rhodes, M., Wiest, D. L. & Vignali, D. A. On the dynamics of TCR:CD3 complex cell surface expression and downmodulation. Immunity 13, 665-675 (2000).
27. Call, M. E. & Wucherpfennig, K. W. The T cell receptor: critical role of the membrane environment in receptor assembly and function. Annu. Rev. Immunol. 23, 101-125 (2005).
28. Allison, K. A. et al. Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells. eLife 5, e10134 (2016).
29. Schietinger, A. & Greenberg, P. D. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 35, 51-60 (2014).
30. Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486-499 (2015).
31. Rivière, I., Brose, K. & Mulligan, R. C. Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells. Proc. Natl Acad. Sci. USA 92, 6733-6737 (1995).
32. Maher, J., Brentjens, R. J., Gunset, G., Rivière, I. & Sadelain, M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRγ /CD28 receptor. Nat. Biotechnol. 20, 70-75 (2002).
33. Gong, M. C. et al. Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen. Neoplasia 1, 123-127 (1999).
34. Gade, T. P. et al. Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res. 65, 9080-9088 (2005).