دورية أكاديمية
أعرض في EDS

A biomaterial platform for T cell-specific gene delivery.

التفاصيل البيبلوغرافية
العنوان: A biomaterial platform for T cell-specific gene delivery.
المؤلفون: Pandit S; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA., Smith BE; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Program in Immunology, Harvard Medical School, Boston, MA, USA., Birnbaum ME; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Brudno Y; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: ybrudno@ncsu.edu.
المصدر: Acta biomaterialia [Acta Biomater] 2024 Mar 15; Vol. 177, pp. 157-164. Date of Electronic Publication: 2024 Feb 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 101233144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-7568 (Electronic) Linking ISSN: 17427061 NLM ISO Abbreviation: Acta Biomater Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Kidlington, Oxford, UK : Elsevier, c2004-
مواضيع طبية MeSH: T-Lymphocytes* , Leukocytes, Mononuclear*, Humans ; Transduction, Genetic ; Genetic Therapy ; Immunotherapy, Adoptive/methods ; Lentivirus/genetics ; Genetic Vectors
مستخلص: Efficient T cell engineering is central to the success of CAR T cell therapy but involves multiple time-consuming manipulations, including T cell isolation, activation, and transduction. These steps add complexity and delay CAR T cell manufacturing, which takes a mean time of 4 weeks. To streamline T cell engineering, we strategically combine two critical engineering solutions - T cell-specific lentiviral vectors and macroporous scaffolds - that enable T cell activation and transduction in a simple, single step. The T cell-specific lentiviral vectors (referred to as STAT virus) target T cells through the display of an anti-CD3 antibody and the CD80 extracellular domain on their surface and provide robust T cell activation. Biocompatible macroporous scaffolds (referred to as Drydux) mediate robust transduction by providing effective interaction between naïve T cells and viral vectors. We show that when unstimulated peripheral blood mononuclear cells (PBMCs) are seeded together with STAT lentivirus on Drydux scaffolds, T cells are activated, selectively transduced, and reprogrammed in a single step. Further, we show that the Drydux platform seeded with PBMCs and STAT lentivirus generates tumor-specific functional CAR T cells. This potent combination of engineered lentivirus and biomaterial scaffold holds promise for an effective, simple, and safe avenue for in vitro and in vivo T cell engineering. STATEMENT OF SIGNIFICANCE: Manufacturing T cell therapies involves lengthy and labor-intensive steps, including T cell selection, activation, and transduction. These steps add complexity to current CAR T cell manufacturing protocols and limit widespread patient access to this revolutionary therapy. In this work, we demonstrate the combination of engineered virus and biomaterial platform that, together, enables selective T cell activation and transduction in a single step, eliminating multistep T cell engineering protocols and significantly simplifying the manufacturing process.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.P., and Y.B. are inventors on patents related to the use of biomaterials for generation of CAR T cell therapeutics. Y.B. receives an industry-sponsored research grant related to CAR T cell therapeutic technology (unrelated to this work). M.E.B. is a co-inventor on a patent related to the lentiviral targeting approach in this manuscript. M.E.B. is a founder, consultant and equity holder of Kelonia Therapeutics and Abata Therapeutics, is an equity holder in 3T Biosciences.
(Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
References: J Vis Exp. 2022 Sep 9;(187):. (PMID: 36156536)
Nat Commun. 2018 Mar 12;9(1):1029. (PMID: 29531262)
Viruses. 2021 Aug 02;13(8):. (PMID: 34452392)
Blood. 2011 Nov 3;118(18):4817-28. (PMID: 21849486)
Cancers (Basel). 2019 Feb 06;11(2):. (PMID: 30736355)
Nat Rev Genet. 2007 Aug;8(8):573-87. (PMID: 17607305)
Nat Methods. 2022 Apr;19(4):449-460. (PMID: 35396484)
Mol Ther Oncolytics. 2016 Jun 15;3:16015. (PMID: 27347557)
Acc Chem Res. 2020 Sep 15;53(9):1749-1760. (PMID: 32786230)
Hum Gene Ther. 2021 Oct;32(19-20):1044-1058. (PMID: 34662233)
Nat Med. 1996 Aug;2(8):876-82. (PMID: 8705856)
Cancer Discov. 2023 Sep 6;13(9):1982-1997. (PMID: 37249512)
Adv Healthc Mater. 2020 Jul;9(14):e2000275. (PMID: 32592454)
Sci Adv. 2022 Apr 8;8(14):eabn8264. (PMID: 35394838)
Front Immunol. 2019 Feb 05;10:128. (PMID: 30804938)
Nat Med. 2018 Oct;24(10):1499-1503. (PMID: 30275568)
Biophys Chem. 2002 Jun 19;97(2-3):159-72. (PMID: 12050007)
Blood Cancer J. 2021 Apr 6;11(4):69. (PMID: 33824268)
Cancers (Basel). 2022 May 27;14(11):. (PMID: 35681646)
Ann Oncol. 2021 Nov;32(11):1366-1380. (PMID: 34375680)
Hum Gene Ther. 2005 Nov;16(11):1241-6. (PMID: 16259557)
Mol Ther Methods Clin Dev. 2022 Jun 09;26:144-156. (PMID: 35795778)
Blood. 2014 Feb 27;123(9):1422-4. (PMID: 24578496)
Hematol Transfus Cell Ther. 2020 Apr - Jun;42(2):150-158. (PMID: 31676276)
Biomaterials. 1997 Apr;18(8):583-90. (PMID: 9134157)
Nat Biomed Eng. 2021 Sep;5(9):1038-1047. (PMID: 33903744)
Blood Adv. 2020 Nov 24;4(22):5702-5715. (PMID: 33216892)
Nat Biotechnol. 2022 Aug;40(8):1250-1258. (PMID: 35332339)
Future Virol. 2014;9(5):483-497. (PMID: 26543491)
Hum Gene Ther. 2019 Dec;30(12):1477-1493. (PMID: 31578886)
Virus Res. 2013 Sep;176(1-2):16-32. (PMID: 23796410)
Bone Marrow Transplant. 2020 Sep;55(9):1706-1715. (PMID: 32474570)
Int J Mol Sci. 2019 Dec 10;20(24):. (PMID: 31835562)
Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7306-11. (PMID: 23589850)
Leukemia. 2018 Jul;32(7):1529-1541. (PMID: 29654266)
J Immunother Cancer. 2022 Dec;10(12):. (PMID: 36549782)
Nat Rev Clin Oncol. 2020 Mar;17(3):147-167. (PMID: 31848460)
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7570-4. (PMID: 7638232)
Biomater Sci. 2023 Mar 28;11(7):2372-2382. (PMID: 36744434)
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11479-84. (PMID: 16864770)
Pharm Res. 2009 Jun;26(6):1432-45. (PMID: 19259792)
معلومات مُعتمدة: DP2 AI158126 United States AI NIAID NIH HHS; P30 CA014051 United States CA NCI NIH HHS; T32 GM007753 United States GM NIGMS NIH HHS; T32 GM144273 United States GM NIGMS NIH HHS; R37 CA260223 United States CA NCI NIH HHS; R21 CA246414 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Alginate; CAR T cell therapy; Gene delivery; Macroporous scaffolds; Pseudotyped lentivirus; T cell activation; T cell engineering; Targeting; Transduction
تواريخ الأحداث: Date Created: 20240216 Date Completed: 20240320 Latest Revision: 20240620
رمز التحديث: 20240620
مُعرف محوري في PubMed: PMC10948289
DOI: 10.1016/j.actbio.2024.02.013
PMID: 38364929
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-7568
DOI:10.1016/j.actbio.2024.02.013