Title:
TRANSGENIC T CELL AND CHIMERIC ANTIGEN RECEPTOR T CELL COMPOSITIONS AND RELATED METHODS
Document Type and Number:
WIPO Patent Application WO/2017/180989
Kind Code:
A3
Abstract:
The invention provides a T cell wherein one or more therapeutic transgenes is integrated at a within the genome of the cell such that expression of the transgene is under control of an endogenous promoter of the T cell. The invention additional provides methods of making and using such cells to treat a subject with T cell therapy. The invention also provides a T cell wherein a recombinant nucleic acid sequence encoding a chimeric antigen receptor (CAR) is integrated at a first site within the genome of the cell such that the CAR is expressed by the cell at the surface of the cell, and wherein integration of the nucleic acid encoding the CAR at the first site reduces or prevents expression of a functional T cell receptor (TCR) complex at the surface of the cell. The invention additional provides methods of making and using such cells to treat a subject with CAR therapy.
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Inventors:
SADELAIN MICHEL W J (US)
EYQUEM JUSTIN GABRIEL ANDRE FRANCOIS (US)
MANSILLA-SOTO JORGE (US)
EYQUEM JUSTIN GABRIEL ANDRE FRANCOIS (US)
MANSILLA-SOTO JORGE (US)
Application Number:
PCT/US2017/027601
Publication Date:
December 14, 2017
Filing Date:
April 14, 2017
Export Citation:
Assignee:
MEMORIAL SLOAN KETTERING CANCER CENTER (US)
International Classes:
C12N5/0783; C07K14/725; C12N9/22; C12N15/63
Domestic Patent References:
| WO2014059173A2 | 2014-04-17 | |||
| WO2015188056A1 | 2015-12-10 | |||
| WO2011011767A1 | 2011-01-27 | |||
| WO2017062439A1 | 2017-04-13 | |||
| WO2017078807A1 | 2017-05-11 | |||
| WO2016081924A1 | 2016-05-26 | |||
| WO2017011519A1 | 2017-01-19 |
Other References:
H. TORIKAI ET AL: "A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR", BLOOD, vol. 119, no. 24, 14 June 2012 (2012-06-14), pages 5697 - 5705, XP055071623, ISSN: 0006-4971, DOI: 10.1182/blood-2012-01-405365
GENE THERAPY ET AL: "Plenary Paper Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome", 22 February 2016 (2016-02-22), XP055397792, Retrieved from the Internet [retrieved on 20170810], DOI: 10.1182/blood-
JUSTIN EYQUEM ET AL: "Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection", NATURE, vol. 543, no. 7643, 22 February 2017 (2017-02-22), pages 113 - 117, XP055397283, ISSN: 0028-0836, DOI: 10.1038/nature21405
DANIEL T. MACLEOD ET AL: "Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells", MOLECULAR THERAPY, vol. 25, no. 4, 23 February 2017 (2017-02-23), US, pages 949 - 961, XP055397282, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2017.02.005
GENE THERAPY ET AL: "Plenary Paper Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome", 22 February 2016 (2016-02-22), XP055397792, Retrieved from the Internet
JUSTIN EYQUEM ET AL: "Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection", NATURE, vol. 543, no. 7643, 22 February 2017 (2017-02-22), pages 113 - 117, XP055397283, ISSN: 0028-0836, DOI: 10.1038/nature21405
DANIEL T. MACLEOD ET AL: "Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells", MOLECULAR THERAPY, vol. 25, no. 4, 23 February 2017 (2017-02-23), US, pages 949 - 961, XP055397282, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2017.02.005
Attorney, Agent or Firm:
ANTLER, Adriane, M. et al. (US)
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