Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.

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Tytuł:: Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.
Autorzy:: Baeuerle PA; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Ding J; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Patel E; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Thorausch N; Department of Immunology, Faculty of Biology, BIOSS Center for Biological Signalling Studies, CIBSS-Centre for Integrative Biological Signalling Studies and Centre for Chronic Immunodeficiency CCI, University of Freiburg, Schänzlestraβe 18, Freiburg, 79104, Germany.
Horton H; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Gierut J; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Scarfo I; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Bldg. 149 13th Street, Charlestown, MA, USA.
Choudhary R; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Kiner O; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Krishnamurthy J; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Le B; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Morath A; Department of Immunology, Faculty of Biology, BIOSS Center for Biological Signalling Studies, CIBSS-Centre for Integrative Biological Signalling Studies and Centre for Chronic Immunodeficiency CCI, University of Freiburg, Schänzlestraβe 18, Freiburg, 79104, Germany.
Baldeviano GC; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Quinn J; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Tavares P; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Wei Q; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Weiler S; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Maus MV; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Bldg. 149 13th Street, Charlestown, MA, USA.
Getts D; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA.
Schamel WW; Department of Immunology, Faculty of Biology, BIOSS Center for Biological Signalling Studies, CIBSS-Centre for Integrative Biological Signalling Studies and Centre for Chronic Immunodeficiency CCI, University of Freiburg, Schänzlestraβe 18, Freiburg, 79104, Germany.
Hofmeister R; TCR² Therapeutics, Inc., 100 Binney Street, Cambridge, MA, 02142, USA. .
Źródło:: Nature communications [Nat Commun] 2019 May 07; Vol. 10 (1), pp. 2087. Date of Electronic Publication: 2019 May 07.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Immunotherapy, Adoptive/*methods
Neoplasms/*therapy
Receptors, Antigen, T-Cell/*immunology
Receptors, Artificial/*immunology
Single-Chain Antibodies/*immunology
T-Lymphocytes/*immunology
Animals ; Antigens, CD19/immunology ; Antigens, Neoplasm/immunology ; Cell Line, Tumor ; Female ; Humans ; Mice ; Mice, Inbred NOD ; Neoplasms/immunology ; Primary Cell Culture ; Protein Domains ; Receptors, Antigen, T-Cell/genetics ; Receptors, Artificial/genetics ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/immunology ; Single-Chain Antibodies/genetics ; Treatment Outcome ; Xenograft Model Antitumor Assays
References:: Crit Care Med. 2017 Feb;45(2):e124-e131. (PMID: 27632680)
Immunity. 1999 Apr;10(4):409-20. (PMID: 10229184)
Nat Med. 2015 Aug;21(8):914-921. (PMID: 26193344)
Immunology. 2018 Jan;153(1):42-50. (PMID: 28771705)
Scand J Immunol. 2008 Apr;67(4):418-20; author reply 421. (PMID: 18282230)
Clin Cancer Res. 1999 Dec;5(12):3928-41. (PMID: 10632322)
Immunity. 2016 May 17;44(5):1091-101. (PMID: 27192576)
Nat Med. 2018 Oct;24(10):1499-1503. (PMID: 30275568)
Immunity. 2007 Jan;26(1):43-54. (PMID: 17188005)
N Engl J Med. 2018 Feb 1;378(5):439-448. (PMID: 29385370)
Hum Gene Ther. 2017 Nov;28(11):1047-1060. (PMID: 28810803)
Cell. 2002 Jun 28;109(7):901-12. (PMID: 12110186)
Nat Biotechnol. 2004 May;22(5):589-94. (PMID: 15064769)
Nat Med. 2015 Jun;21(6):581-90. (PMID: 25939063)
Blood. 2017 Jun 22;129(25):3322-3331. (PMID: 28408462)
Nat Rev Immunol. 2008 Sep;8(9):699-712. (PMID: 18728635)
Mol Ther. 2017 Jan 4;25(1):285-295. (PMID: 28129122)
Immunol Lett. 2008 Mar 15;116(2):203-10. (PMID: 18215426)
J Immunol. 1993 Apr 1;150(7):2675-86. (PMID: 7681078)
Cancer Immunol Res. 2015 Apr;3(4):356-67. (PMID: 25600436)
Int Immunol. 2004 Jul;16(7):889-94. (PMID: 15148288)
Blood. 2015 Jun 25;125(26):4017-23. (PMID: 25999455)
J Immunol. 2017 Sep 1;199(5):1555-1560. (PMID: 28733484)
J Exp Med. 1986 Jul 1;164(1):90-103. (PMID: 3088203)
J Exp Med. 2005 Aug 15;202(4):493-503. (PMID: 16087711)
Cancer Discov. 2016 Jun;6(6):664-79. (PMID: 27076371)
Cell Res. 2017 Jan;27(1):38-58. (PMID: 28025979)
Nature. 2005 Jul 28;436(7050):578-82. (PMID: 16049493)
Nat Immunol. 2010 Jan;11(1):90-6. (PMID: 20010844)
Anal Biochem. 1994 Mar;217(2):220-30. (PMID: 8203750)
Front Immunol. 2017 Apr 03;8:267. (PMID: 28421069)
J Immunol. 2013 Mar 1;190(5):1927-35. (PMID: 23359496)
EMBO Rep. 2006 May;7(5):490-5. (PMID: 16670682)
J Immunol. 2017 Jan 1;198(1):47-52. (PMID: 27994168)
Nature. 1989 Mar 30;338(6214):383-4. (PMID: 2927501)
Cancer Immunol Res. 2016 Aug;4(8):669-78. (PMID: 27312342)
Cancer Immunol Res. 2015 Jul;3(7):815-26. (PMID: 25941351)
Annu Rev Immunol. 1988;6:629-62. (PMID: 3289580)
Nat Struct Biol. 2000 Nov;7(11):1023-6. (PMID: 11062556)
Eur J Immunol. 1993 Jul;23(7):1636-42. (PMID: 7686857)
Cell. 2002 Dec 27;111(7):967-79. (PMID: 12507424)
Clin Cancer Res. 2015 Sep 15;21(18):4062-72. (PMID: 26059190)
Nature. 1982 Nov 4;300(5887):66-9. (PMID: 6982419)
J Biol Chem. 2009 Sep 18;284(38):26096-105. (PMID: 19628870)
N Engl J Med. 2018 Feb 1;378(5):449-459. (PMID: 29385376)
N Engl J Med. 2017 Dec 28;377(26):2531-2544. (PMID: 29226797)
Immunity. 2011 Sep 23;35(3):375-87. (PMID: 21903423)
J Immunol. 2008 May 1;180(9):6116-31. (PMID: 18424733)
Sci Signal. 2014 Dec 02;7(354):ra115. (PMID: 25468995)
Nat Immunol. 2014 Sep;15(9):790-7. (PMID: 25137453)
Immunity. 2015 Aug 18;43(2):227-39. (PMID: 26231119)
Substance Nomenclature:: 0 (Antigens, CD19)
0 (Antigens, Neoplasm)
0 (Receptors, Antigen, T-Cell)
0 (Receptors, Artificial)
0 (Recombinant Fusion Proteins)
0 (Single-Chain Antibodies)
Entry Date(s):: Date Created: 20190509 Date Completed: 20190610 Latest Revision: 20210109
Update Code:: 20240105
PubMed Central ID:: PMC6504948
DOI:: 10.1038/s41467-019-10097-0
PMID:: 31064990
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T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner.

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