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Methods for enhancing in vivo persistence and efficacy of exogenously administered t cells, genetically modified t cells and method and method of use

An exogenous, cellular technology, applied in receptor/cell surface antigen/cell surface determinant, chemical instruments and methods, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc. instability, etc.

Active Publication Date: 2018-08-31
BEIHAO STEM CELL & REGENERATIVE MEDICINE RES INST CO LTD +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, genomic integration and constitutive expression of the TERT transgene lead to chromosomal instability [Zhou et al., J Immunol., 175:7046-7052 (2005); Bennaceur, Atherosclerosis, 236:312-320 (2014); Verra et al., Cancer Res., 64:2153-2161 (2004); Barsov et al., Immunotherapy, 3:407-421 (2011)], which raises safety issues in clinical application

Method used

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  • Methods for enhancing in vivo persistence and efficacy of exogenously administered t cells, genetically modified t cells and method and method of use
  • Methods for enhancing in vivo persistence and efficacy of exogenously administered t cells, genetically modified t cells and method and method of use
  • Methods for enhancing in vivo persistence and efficacy of exogenously administered t cells, genetically modified t cells and method and method of use

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Embodiment

[0080] Materials and methods

[0081] culture medium

[0082] T cells were cultured in T cell medium containing: X-VIVO™ 15 medium (Lonza, Basel, CH) supplemented with 5% fetal bovine serum (FBS) (Gibco, LAX, CA, USA), 100 U / mL Penicillin, 100 μg / mL streptomycin, 1.25 μg / mL amphotericin B, 2 mM L-glutamine (Gibco, CA, USA) and 100 U / mL hIL-2 (PerproTech, Rocky Hill, USA). T cells were activated using CD3- and CD28-specific magnetic beads (Invitrogen Life Technologies, Carlsbad, CA, USA) at 3 beads / cell. Raji and K562 cells were cultured in R10 medium containing: Roswell Park Memorial Institute (RPMI) 1640 (Hyclone, Logan, Utah, USA), supplemented with 10% fetal bovine serum (FBS), 100 U / mL penicillin, 100 μg / mL Streptomycin (Gibco, CA, USA) and 2 mM L-glutamine (Gibco, CA, USA). 293T cells were cultured in D10 medium containing: Dulbecco's modified Eagle's medium (Hyclone, UT, USA) supplemented with 10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin and 2 mM L-glutamine ...

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Abstract

A method for enhancing the in vitro and in vivo lifespan of T cells is provided. A method for enhancing the life span of a T cell is provided. The method includes engineering the T cell to express exogenous ribonucleic acid (RNA), where the RNA includes a nucleic acid encoding telomerase reverse transcriptase (TERT). T cells genetically engineered to transiently express exogenous RNA which includes the coding sequence for TERT (TERT T cells) are provided. TERT T cells have one or more of the following characteristics when compared to a T cells not expressing TERT from an exogenously introducednucleotide: enhanced in vitro and in vivo proliferation, decreased number of senescent cells, and enhanced in vivo anti-cancer activity. The modified TERT T cells can be used in adoptive cell transfer to treat a subject in need thereof.

Description

field of invention [0001] The present invention is generally in the field of adoptive cell therapy and relates to methods for enhancing the in vivo persistence and efficacy of exogenously administered T cells. Background of the invention [0002] Recently, chimeric antigen receptor (CAR)-T cell immunotherapy has emerged as a promising approach for the treatment of tumors (Cheadle, Methods Mol Biol, 907:645-666 (2012); Restifo, Nat Rev Immunol, 12:269- 281 (2012)), and this therapeutic strategy has shown significant advantages over traditional T cell immunotherapy. Expression of CAR in T lymphocytes confers the ability to recognize specific tumor antigens (Jensen et al., Curr Opin Immunol, 33:9-15 (2015)). Furthermore, CAR specifically redirects T cells in an HLA (human leukocyte antigen)-independent manner, thereby eliminating the need to consider HLA restrictions and overcoming some tumor escape mechanisms (Ramos et al., Expert Opin BiolTher, 11:855 -873 (2011)). Importa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0783A61K39/00A61P35/00
CPCC07K16/2803C07K16/30C07K2317/622C07K2319/03C07K2319/33C12N2740/15043A61P35/00C07K14/7051A61K39/464412A61K2239/48A61K39/4631A61K39/464457A61K39/4611
Inventor 邓宏魁白云文锦华阚士风周士新
Owner BEIHAO STEM CELL & REGENERATIVE MEDICINE RES INST CO LTD
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