Title:
COMPOSITIONS AND METHODS FOR INHIBITING T CELL EXHAUSTION
Document Type and Number:
WIPO Patent Application WO/2019/118902
Kind Code:
A3
Abstract:
The present invention relates to T cell compositions and methods of using the same in the context of therapy and treatment. In particular, the invention provides T cells that are modified (e.g., genetically and/or functionally) to maintain functionality under conditions in which unmodified T cells display exhaustion. Compositions and methods disclosed herein find use in preventing exhaustion of engineered (e.g., chimeric antigen receptor (CAR) T cells) as well as non-engineered T cells thereby enhancing T cell function (e.g., activity against cancer or infectious disease).
Inventors:
MACKALL CRYSTAL (US)
LYNN RACHEL (US)
WEBER EVAN (US)
SOTILLO ELENA (US)
LYNN RACHEL (US)
WEBER EVAN (US)
SOTILLO ELENA (US)
Application Number:
PCT/US2018/065801
Publication Date:
July 18, 2019
Filing Date:
December 14, 2018
Export Citation:
Assignee:
UNIV LELAND STANFORD JUNIOR (US)
International Classes:
A61K35/17; A61P35/00; C12N5/0783; C12N5/10
Domestic Patent References:
| WO2016179283A1 | 2016-11-10 | |||
| WO2015164594A1 | 2015-10-29 |
Foreign References:
| US20160317654A1 | 2016-11-03 |
Other References:
BEHRENS, A ET AL.: "Jun N-terminal kinase 2 modulates thymocyte apoptosis and T cell activation through c-Jun and nuclear factor of activated T cell (NF- AT", PNAS- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE U.S.A., vol. 98, no. 4, 13 February 2001 (2001-02-13), pages 1769 - 1774, XP055623937
FINCH, S ET AL.: "JunB negatively regulates AP -1 activity and cell proliferation of malignant mouse keratinocytes", JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, vol. 128, no. 1, January 2002 (2002-01-01), pages 3 - 10, XP055623945
JURADO, J ET AL.: "Alternative splicing of c-fos pre-mRNA: contribution of the rates of synthesis and degradation to the copy number of each transcript isoform and detection of a truncated c-Fos immunoreactive species", BMC MOLECULAR BIOLOGY, vol. 8, no. 83, 21 September 2007 (2007-09-21), pages 1 - 14, XP021033428
LIANG, G ET AL.: "Characterization of Human Activating Transcription Factor 4, a Transcriptional Activator That Interacts with Multiple Domains of cAMP-responsive Element-binding Protein (CREB)-binding Protein (CBP", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 38, 19 September 1997 (1997-09-19), pages 24088 - 24095, XP002148211, doi:10.1074/jbc.272.38.24088
FAHMY, TM ET AL.: "Increased TCR Avidity after T Cell Activation: A Mechanism for Sensing Low-Density Antigen", IMMUNITY, vol. 14, no. 2, 1 February 2001 (2001-02-01), pages 135 - 143, XP055623957
HU , G ET AL.: "A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD 8+ T Cell Development", NATURE COMMUNICATIONS, vol. 4, no. 2830, 2013 - 25 April 2014 (2014-04-25), pages 1 - 30, XP055623960
FOLETTA, VC ET AL.: "Transcriptional regulation in the immune system: all roads lead to AP -1", JOURNAL OF LEUKOCYTE BIOLOGY, vol. 63, no. 2, February 1998 (1998-02-01), pages 139 - 152, XP002927645
FINCH, S ET AL.: "JunB negatively regulates AP -1 activity and cell proliferation of malignant mouse keratinocytes", JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, vol. 128, no. 1, January 2002 (2002-01-01), pages 3 - 10, XP055623945
JURADO, J ET AL.: "Alternative splicing of c-fos pre-mRNA: contribution of the rates of synthesis and degradation to the copy number of each transcript isoform and detection of a truncated c-Fos immunoreactive species", BMC MOLECULAR BIOLOGY, vol. 8, no. 83, 21 September 2007 (2007-09-21), pages 1 - 14, XP021033428
LIANG, G ET AL.: "Characterization of Human Activating Transcription Factor 4, a Transcriptional Activator That Interacts with Multiple Domains of cAMP-responsive Element-binding Protein (CREB)-binding Protein (CBP", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 38, 19 September 1997 (1997-09-19), pages 24088 - 24095, XP002148211, doi:10.1074/jbc.272.38.24088
FAHMY, TM ET AL.: "Increased TCR Avidity after T Cell Activation: A Mechanism for Sensing Low-Density Antigen", IMMUNITY, vol. 14, no. 2, 1 February 2001 (2001-02-01), pages 135 - 143, XP055623957
HU , G ET AL.: "A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD 8+ T Cell Development", NATURE COMMUNICATIONS, vol. 4, no. 2830, 2013 - 25 April 2014 (2014-04-25), pages 1 - 30, XP055623960
FOLETTA, VC ET AL.: "Transcriptional regulation in the immune system: all roads lead to AP -1", JOURNAL OF LEUKOCYTE BIOLOGY, vol. 63, no. 2, February 1998 (1998-02-01), pages 139 - 152, XP002927645
Attorney, Agent or Firm:
GOETZ, Robert A. (US)
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