Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation

Wu Yu; Li Peilu; Ge Jun; Jiang Tingya

doi:10.3969/j.issn.1674-7445.2020.05.003

Volume 11 Issue 5

Sep. 2020

Turn off MathJax

Article Contents

Article Navigation > ORGAN TRANSPLANTATION > 2020 > 11(5): 547-552

Wu Yu, Li Peilu, Ge Jun, et al. Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation[J]. ORGAN TRANSPLANTATION, 2020, 11(5): 547-552. doi: 10.3969/j.issn.1674-7445.2020.05.003

Citation:

PDF( 1052 KB)

Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation

doi: 10.3969/j.issn.1674-7445.2020.05.003

Wu Yu^1
,,
Li Peilu²,
Ge Jun^{1, 2},
Jiang Tingya^{1
,
,}

1.
AlloDx Biotech Co., LTD, Shanghai 215000, China

More Information

Corresponding author: Jiang Tingya, Email: jiangtingya@allograftdx.com
Received Date: 2020-05-23
Available Online: 2021-01-19
Publish Date: 2020-09-15

Abstract

Abstract

Regulatory T cell (Treg) is a subset of T cells that negatively regulates immunity and has the function of inhibiting rejection. The specific modification of Treg by chimeric antigen receptor (CAR) technology can successfully chime donor-specific antigen onto the surface of Treg, thus regulating the immune function of the body in a real-time manner. It provides a novel and promising therapeutic option for inducing immune tolerance. In this article, research progresses on Treg in immune related diseases, main difficulties in the realization of CAR-Treg technology and its role in inducing transplantation immune tolerance were reviewed, and the opportunities and challenges of CAR-Treg application in the field of organ transplantation are prospected.

FullText(HTML)

References(39)

References

[1]	SELLARÉS J, DE FREITAS DG, MENGEL M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence[J]. Am J Transplant, 2012, 12(2):388-399. DOI: 10.1111/j.1600-6143.2011.03840.x.
[2]	FARKASH EA, COLVIN RB. Diagnostic challenges in chronic antibody-mediated rejection[J]. Nat Rev Nephrol, 2012, 8(5):255-257. DOI: 10.1038/nrneph.2012.61.
[3]	MATSUDA Y, SARWAL MM. Unraveling the role of allo-antibodies and transplant injury[J]. Front Immunol, 2016, 7:432. DOI: 10.3389/fimmu.2016.00432.
[4]	GONZÁLEZ-GALARZA FF, TAKESHITA LY, SANTOS EJ, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations[J]. Nucleic Acids Res, 2015, 43(Database issue):D784-D788. DOI: 10.1093/nar/gku1166.
[5]	中华医学会器官移植学分会.器官移植免疫抑制剂临床应用技术规范(2019版)[J].器官移植, 2019, 10(3): 213-226. DOI: 10.3969/j.issn.1674-7445.2019.03.001. Branch of Organ Transplantation of Chinese Medical Association. Technical specifcation for clinical application of immunosuppressive agents in organ transplantation (2019 edition)[J]. Organ Transplant, 2019, 10(3): 213-226. DOI: 10.3969/j.issn.1674-7445.2019.03.001.
[6]	SIKMA MA, VAN MAARSEVEEN EM, VAN DE GRAAF EA, et al. Pharmacokinetics and toxicity of tacrolimus early after heart and lung transplantation[J]. Am J Transplant, 2015, 15(9):2301-2313. DOI: 10.1111/ajt.13309.
[7]	ANDREWS LM, LI Y, DE WINTER BCM, et al. Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients[J]. Expert Opin Drug Metab Toxicol, 2017, 13(12):1225-1236. DOI: 10.1080/17425255.2017.1395413.
[8]	BENNETT CL, CHRISTIE J, RAMSDELL F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of Foxp3[J]. Nat Genet, 2001, 27(1):20-21. DOI: 10.1038/83713.
[9]	BRUNKOW ME, JEFFERY EW, HJERRILD KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse[J]. Nat Genet, 2001, 27(1):68-73. DOI: 10.1038/83784.
[10]	ROMANO M, TUNG SL, SMYTH LA, et al. Treg therapy in transplantation: a general overview[J]. Transpl Int, 2017, 30(8):745-753. DOI: 10.1111/tri.12909.
[11]	VAIKUNTHANATHAN T, SAFINIA N, BOARDMAN D, et al. Regulatory T cells: tolerance induction in solid organ transplantation[J]. Clin Exp Immunol, 2017, 189(2):197-210. DOI: 10.1111/cei.12978.
[12]	SAKAGUCHI S, TAKAHASHI T, YAMAZAKI S, et al. Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity[J]. Microbes Infect, 2001, 3(11):911-918. DOI: 10.1016/s1286-4579(01)01452-6.
[13]	SAKAGUCHI S, SAKAGUCHI N, ASANO M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. J Immunol, 1995, 155(3):1151-1164.
[14]	WEBER SE, HARBERTSON J, GODEBU E, et al. Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo[J]. J Immunol, 2006, 176(8):4730-4739. DOI: 10.4049/jimmunol.176.8.4730.
[15]	BISWAS M, KUMAR SRP, TERHORST C, et al. Gene therapy with regulatory T cells: a beneficial alliance[J]. Front Immunol, 2018, 9:554. DOI: 10.3389/fimmu.2018.00554.
[16]	TRZONKOWSKI P, SZARYŃSKA M, MYŚLIWSKA J, et al. Ex vivo expansion of CD4(+)CD25(+) T regulatory cells for immunosuppressive therapy[J]. Cytometry A, 2009, 75(3):175-188. DOI: 10.1002/cyto.a.20659.
[17]	DI IANNI M, FALZETTI F, CAROTTI A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation[J]. Blood, 2011, 117(14):3921-3928.DOI: 10.1182/blood-2010-10-311894.
[18]	THEIL A, TUVE S, OELSCHLÄGEL U, et al. Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease[J]. Cytotherapy, 2015, 17(4):473-486. DOI: 10.1016/j.jcyt.2014.11.005.
[19]	WHITEHOUSE GP, HOPE A, SANCHEZ-FUEYO A. Regulatory T-cell therapy in liver transplantation[J]. Transpl Int, 2017, 30(8):776-784. DOI: 10.1111/tri.12998.
[20]	BLUESTONE JA, BUCKNER JH, FITCH M, et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells[J]. Sci Transl Med, 2015, 7(315):315ra189. DOI: 10.1126/scitranslmed.aad4134.
[21]	ZHANG Q, LU W, LIANG CL, et al. Chimeric antigen receptor (CAR) Treg: a promising approach to inducing immunological tolerance[J]. Front Immunol, 2018, 9:2359. DOI: 10.3389/fimmu.2018.02359.
[22]	TRZONKOWSKI P, BIENIASZEWSKA M, JUŚCIŃSKA J, et al. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4⁺CD25⁺CD127^-T regulatory cells[J]. Clin Immunol, 2009, 133(1):22-26. DOI: 10.1016/j.clim.2009.06.001.
[23]	MACDONALD KG, HOEPPLI RE, HUANG Q, et al. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor[J]. J Clin Invest, 2016, 126(4):1413-1424. DOI: 10.1172/JCI82771.
[24]	BÉZIE S, CHARREAU B, VIMOND N, et al. Human CD8⁺ Tregs expressing a MHC-specific CAR display enhanced suppression of human skin rejection and GVHD in NSG mice[J]. Blood Adv, 2019, 3(22):3522-3538. DOI: 10.1182/bloodadvances.2019000411.
[25]	BATTAGLIA M, STABILINI A, DRAGHICI E, et al. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance[J]. Diabetes, 2006, 55(1):40-49.
[26]	BATTAGLIA M, STABILINI A, MIGLIAVACCA B, et al. Rapamycin promotes expansion of functional CD4⁺CD25⁺Foxp3⁺ regulatory T cells of both healthy subjects and type 1 diabetic patients[J]. J Immunol, 2006, 177(12):8338-8347.DOI: 10.4049/jimmunol.177.12.8338.
[27]	ABOU-EL-ENEIN M, BAUER G, MEDCALF N, et al. Putting a price tag on novel autologous cellular therapies[J]. Cytotherapy, 2016, 18(8):1056-1061. DOI: 10.1016/j.jcyt.2016.05.005.
[28]	ABOU-EL-ENEIN M, VOLK HD, REINKE P. Clinical development of cell therapies: setting the stage for academic success[J]. Clin Pharmacol Ther, 2017, 101(1):35-38. DOI: 10.1002/cpt.523.
[29]	MATHEW JM, H-VOSS J, LEFEVER A, et al. A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants[J]. Sci Rep, 2018, 8(1):7428. DOI: 10.1038/s41598-018-25574-7.
[30]	FRITSCHE E, VOLK HD, REINKE P, et al. Toward an optimized process for clinical manufacturing of CAR-Treg cell therapy[J]. Trends Biotechnol, 2020, DOI: 10.1016/j.tibtech.2019.12.009[Epubahead of print].
[31]	HORWITZ DA, PAN S, OU JN, et al. Therapeutic polyclonal human CD8⁺CD25⁺Fox3⁺TNFR2⁺PD-L1⁺ regulatory cells induced ex-vivo[J]. Clin Immunol, 2013, 149(3):450-463. DOI: 10.1016/j.clim.2013.08.007.
[32]	PLUSCHKE J, KLAUSING S, HASELOFF A, et al. Determination of intracellular antibody production, cell density, and viability of recombinant CHO-DG44 cells using the MACSQuant^Ⓡ Analyzer[J]. BMC Proc, 2011, 5 (Suppl 8):P97. DOI: 10.1186/1753-6561-5-S8-P97.
[33]	MARÍN MORALES JM, MÜNCH N, PETER K, et al. Automated clinical grade expansion of regulatory T cells in a fully closed system[J]. Front Immunol, 2019, 10:38. DOI: 10.3389/fimmu.2019.00038.
[34]	RAMANAYAKE S, BILMON I, BISHOP D, et al. Low-cost generation of good manufacturing practice-grade CD19-specific chimeric antigen receptor-expressing T cells using piggyBac gene transfer and patient-derived materials[J]. Cytotherapy, 2015, 17(9):1251-1267. DOI: 10.1016/j.jcyt.2015.05.013.
[35]	SINGH H, HULS H, KEBRIAEI P, et al. A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19[J]. Immunol Rev, 2014, 257(1):181-190. DOI: 10.1111/imr.12137.
[36]	SÁNCHEZ-FUEYO A, WHITEHOUSE G, GRAGEDA N, et al. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation[J]. Am J Transplant, 2020, 20(4):1125-1136. DOI: 10.1111/ajt.15700.
[37]	BOARDMAN DA, PHILIPPEOS C, FRUHWIRTH GO, et al. Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection[J]. Am J Transplant, 2017, 17(4):931-943. DOI: 10.1111/ajt.14185.
[38]	SICARD A, LAMARCHE C, SPECK M, et al. Donor-specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients[J]. Am J Transplant, 2020, 20(6):1562-1573. DOI: 10.1111/ajt.15787.
[39]	BOROUGHS AC, LARSON RC, CHOI BD, et al. Chimeric antigen receptor costimulation domains modulate human regulatory T cell function[J]. JCI Insight, 2019, 5(8):e126194. DOI: 10.1172/jci.insight.126194.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1)

Get Citation

PDF

XML

Article Metrics

Article views (309) PDF downloads(50)

Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation

doi: 10.3969/j.issn.1674-7445.2020.05.003

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation

doi: 10.3969/j.issn.1674-7445.2020.05.003

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Export File

Citation

Format

Content