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Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains

Gene Therapy volume 19, pages 365–374 (2012)Cite this article

Abstract

Transduction of exogenous T-cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These ‘mixed’ heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not eliminate the formation of mixed heterodimers. By contrast, deletion of the constant regions, through use of a stabilized Vα/Vβ single-chain TCR (scTv), avoided mispairing completely. By linking a high-affinity scTv to intracellular signaling domains, such as Lck and CD28, the scTv was capable of activating functional T-cell responses in the absence of either the CD3 subunits or the co-receptors, and circumvented mispairing with endogenous TCRs. Such transduced T cells can respond to the targeted antigen independent of CD3 subunits via the introduced scTv, without the transduced T cells acquiring any new undefined and potentially dangerous specificities.

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References

  1. Bendle GM, Haanen JB, Schumacher TN . Preclinical development of T cell receptor gene therapy. Curr Opin Immunol 2009; 21: 209–214.

    Article  CAS  Google Scholar 

  2. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–129.

    Article  CAS  Google Scholar 

  3. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009; 114: 535–546.

    Article  CAS  Google Scholar 

  4. Bendle GM, Linnemann C, Hooijkaas AI, Bies L, de Witte MA, Jorritsma A et al. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 2010; 16: 565–570, 561p following 570.

    Article  CAS  Google Scholar 

  5. Davis MM, Boniface JJ, Reich Z, Lyons D, Hampl J, Arden B et al. Ligand recognition by alpha beta T cell receptors. Annu Rev Immunol 1998; 16: 523–544.

    Article  CAS  Google Scholar 

  6. Sarukhan A, Garcia C, Lanoue A, von Boehmer H . Allelic inclusion of T cell receptor alpha genes poses an autoimmune hazard due to low-level expression of autospecific receptors. Immunity 1998; 8: 563–570.

    Article  CAS  Google Scholar 

  7. Willemsen RA, Weijtens ME, Ronteltap C, Eshhar Z, Gratama JW, Chames P et al. Grafting primary human T lymphocytes with cancer-specific chimeric single chain and two chain TCR. Gene Therapy 2000; 7: 1369–1377.

    Article  CAS  Google Scholar 

  8. Schumacher TN . T-cell-receptor gene therapy. Nat Rev Immunol 2002; 2: 512–519.

    Article  CAS  Google Scholar 

  9. Schmitt TM, Ragnarsson GB, Greenberg PD . T cell receptor gene therapy for cancer. Hum Gene Ther 2009; 20: 1240–1248.

    Article  CAS  Google Scholar 

  10. van Loenen MM, de Boer R, Amir AL, Hagedoorn RS, Volbeda GL, Willemze R et al. Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc Natl Acad Sci USA 2010; 107: 10972–10977.

    Article  CAS  Google Scholar 

  11. Engels B, Uckert W . Redirecting T lymphocyte specificity by T cell receptor gene transfer—a new era for immunotherapy. Mol Aspects Med 2007; 28: 115–142.

    Article  CAS  Google Scholar 

  12. Heemskerk MH, Hagedoorn RS, van der Hoorn MA, van der Veken LT, Hoogeboom M, Kester MG et al. Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex. Blood 2007; 109: 235–243.

    Article  CAS  Google Scholar 

  13. Sommermeyer D, Neudorfer J, Weinhold M, Leisegang M, Engels B, Noessner E et al. Designer T cells by T cell receptor replacement. Eur J Immunol 2006; 36: 3052–3059.

    Article  CAS  Google Scholar 

  14. Govers C, Sebestyen Z, Coccoris M, Willemsen RA, Debets R . T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol Med 2010; 16: 77–87.

    Article  CAS  Google Scholar 

  15. Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA . Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res 2006; 66: 8878–8886.

    Article  CAS  Google Scholar 

  16. Sebestyen Z, Schooten E, Sals T, Zaldivar I, San Jose E, Alarcon B et al. Human TCR that incorporate CD3zeta induce highly preferred pairing between TCRalpha and beta chains following gene transfer. J Immunol 2008; 180: 7736–7746.

    Article  CAS  Google Scholar 

  17. Boulter JM, Glick M, Todorov PT, Baston E, Sami M, Rizkallah P et al. Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng 2003; 16: 707–711.

    Article  CAS  Google Scholar 

  18. Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 2007; 109: 2331–2338.

    Article  CAS  Google Scholar 

  19. Cohen CJ, Li YF, El-Gamil M, Robbins PF, Rosenberg SA, Morgan RA . Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 2007; 67: 3898–3903.

    Article  CAS  Google Scholar 

  20. Thomas S, Xue SA, Cesco-Gaspere M, San Jose E, Hart DP, Wong V et al. Targeting the Wilms tumor antigen 1 by TCR gene transfer: TCR variants improve tetramer binding but not the function of gene modified human T cells. J Immunol 2007; 179: 5803–5810.

    Article  CAS  Google Scholar 

  21. Ohashi PS, Mak TW, Van den Elsen P, Yanagi Y, Yoshikai Y, Calman AF et al. Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. Nature 1985; 316: 606–609.

    Article  CAS  Google Scholar 

  22. Minami Y, Weissman AM, Samelson LE, Klausner RD . Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor. Proc Natl Acad Sci USA 1987; 84: 2688–2692.

    Article  CAS  Google Scholar 

  23. Schodin BA, Tsomides TJ, Kranz DM . Correlation between the number of T cell receptors required for T cell activation and TCR-ligand affinity. Immunity 1996; 5: 137–146.

    Article  CAS  Google Scholar 

  24. Jorritsma A, Gomez-Eerland R, Dokter M, van de Kasteele W, Zoet YM, Doxiadis II et al. Selecting highly affine and well-expressed TCRs for gene therapy of melanoma. Blood 2007; 110: 3564–3572.

    Article  CAS  Google Scholar 

  25. de Witte MA, Jorritsma A, Kaiser A, van den Boom MD, Dokter M, Bendle GM et al. Requirements for effective antitumor responses of TCR transduced T cells. J Immunol 2008; 181: 5128–5136.

    Article  CAS  Google Scholar 

  26. Sommermeyer D, Uckert W . Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR gene-modified T cells. J Immunol 2010; 184: 6223–6231.

    Article  CAS  Google Scholar 

  27. Zhang T, He X, Tsang TC, Harris DT . Transgenic TCR expression: comparison of single chain with full-length receptor constructs for T-cell function. Cancer Gene Ther 2004; 11: 487–496.

    Article  CAS  Google Scholar 

  28. Schaft N, Lankiewicz B, Drexhage J, Berrevoets C, Moss DJ, Levitsky V et al. T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. Int Immunol 2006; 18: 591–601.

    Article  CAS  Google Scholar 

  29. Voss RH, Thomas S, Pfirschke C, Hauptrock B, Klobuch S, Kuball J et al. Coexpression of the T-cell receptor constant alpha domain triggers tumor reactivity of single chain TCR transduced human T cells. Blood 2010; 115: 5154–5163.

    Article  CAS  Google Scholar 

  30. Richman SA, Aggen DH, Dossett ML, Donermeyer DL, Allen PM, Greenberg PD et al. Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain ValphaVbeta fragments. Mol Immunol 2009; 46: 902–916.

    Article  CAS  Google Scholar 

  31. Schodin BA, Kranz DM . Binding affinity and inhibitory properties of a single-chain anti-T cell receptor antibody. J Biol Chem 1993; 268: 25722–25727.

    CAS  PubMed  Google Scholar 

  32. Holler PD, Chlewicki LK, Kranz DM . TCRs with high affinity for foreign pMHC show self-reactivity. Nat Immunol 2003; 4: 55–62.

    Article  CAS  Google Scholar 

  33. Chervin AS, Aggen DH, Raseman JM, Kranz DM . Engineering higher affinity T cell receptors using a T cell display system. J Immunol Methods 2008; 339: 175–184.

    Article  CAS  Google Scholar 

  34. Cho BK, Lian KC, Lee P, Brunmark A, McKinley C, Chen J et al. Differences in antigen recognition and cytolytic activity of CD8(+) and CD8(−) T cells that express the same antigen-specific receptor. Proc Natl Acad Sci USA 2001; 98: 1723–1727.

    Article  CAS  Google Scholar 

  35. Sadelain M, Brentjens R, Riviere I . The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol 2009; 21: 215–223.

    Article  CAS  Google Scholar 

  36. Kieke MC, Shusta EV, Boder ET, Teyton L, Wittrup KD, Kranz DM . Selection of functional T cell receptor mutants from a yeast surface- display library. Proc Natl Acad Sci USA 1999; 96: 5651–5656.

    Article  CAS  Google Scholar 

  37. Weber KS, Donermeyer DL, Allen PM, Kranz DM . Class II-restricted T cell receptor engineered in vitro for higher affinity retains peptide specificity and function. Proc Natl Acad Sci USA 2005; 102: 19033–19038.

    Article  CAS  Google Scholar 

  38. Geiger TL, Nguyen P, Leitenberg D, Flavell RA . Integrated src kinase and costimulatory activity enhances signal transduction through single-chain chimeric receptors in T lymphocytes. Blood 2001; 98: 2364–2371.

    Article  CAS  Google Scholar 

  39. Daniels MA, Jameson SC . Critical role for CD8 in T cell receptor binding and activation by Peptide/Major histocompatibility complex multimers. J Exp Med 2000; 191: 335–346.

    Article  CAS  Google Scholar 

  40. Chervin AS, Stone JD, Holler PD, Bai A, Chen J, Eisen HN et al. The impact of TCR-binding properties and antigen presentation format on T cell responsiveness. J Immunol 2009; 183: 1166–1178.

    Article  CAS  Google Scholar 

  41. Letourneur F, Malissen B . Derivation of a T cell hybridoma variant deprived of functional T cell receptor alpha and beta chain transcripts reveals a nonfunctional alpha- mRNA of BW5147 origin. Eur J Immunol 1989; 19: 2269–2274.

    Article  CAS  Google Scholar 

  42. Holler PD, Kranz DM . Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation. Immunity 2003; 18: 255–264.

    Article  CAS  Google Scholar 

  43. Ma Z, Sharp KA, Janmey PA, Finkel TH . Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. PLoS Biol 2008; 6: e43.

    Article  Google Scholar 

  44. Varela-Rohena A, Molloy PE, Dunn SM, Li Y, Suhoski MM, Carroll RG et al. Control of HIV-1 immune escape by CD8T cells expressing enhanced T-cell receptor. Nat Med 2008; 14: 1390–1395.

    Article  CAS  Google Scholar 

  45. Aggen DH, Chervin AS, Insaidoo FK, Piepenbrink KH, Baker BM, Kranz DM . Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors. Protein Engineer Design Selection 2011; 24: 361–372.

    Article  CAS  Google Scholar 

  46. Badowski MS, Zhang T, Tsang TC, Harris DT . Chimeric antigen receptors for stem cell based immunotherapy. J Exp Ther Oncol 2009; 8: 53–63.

    CAS  PubMed  Google Scholar 

  47. Ji Q, Perchellet A, Goverman JM . Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol 2010; 11: 628–634.

    Article  CAS  Google Scholar 

  48. Scholten KB, Kramer D, Kueter EW, Graf M, Schoedl T, Meijer CJ et al. Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin Immunol 2006; 119: 135–145.

    Article  CAS  Google Scholar 

  49. Holst J, Vignali KM, Burton AR, Vignali DA . Rapid analysis of T-cell selection in vivo using T cell-receptor retrogenic mice. Nat Methods 2006; 3: 191–197.

    Article  CAS  Google Scholar 

  50. Leisegang M, Engels B, Meyerhuber P, Kieback E, Sommermeyer D, Xue SA et al. Enhanced functionality of T cell receptor-redirected T cells is defined by the transgene cassette. J Mol Med 2008; 86: 573–583.

    Article  CAS  Google Scholar 

  51. Voss RH, Willemsen RA, Kuball J, Grabowski M, Engel R, Intan RS et al. Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 2008; 180: 391–401.

    Article  CAS  Google Scholar 

  52. Bialer G, Horovitz-Fried M, Ya’acobi S, Morgan RA, Cohen CJ . Selected murine residues endow human TCR with enhanced tumor recognition. J Immunol 2010; 184: 6232–6241.

    Article  CAS  Google Scholar 

  53. Frankel TL, Burns WR, Peng PD, Yu Z, Chinnasamy D, Wargo JA et al. Both CD4 and CD8T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase. J Immunol 2010; 184: 5988–5998.

    Article  CAS  Google Scholar 

  54. Goff SL, Johnson LA, Black MA, Xu H, Zheng Z, Cohen CJ et al. Enhanced receptor expression and in vitro effector function of a murine-human hybrid MART-1-reactive T cell receptor following a rapid expansion. Cancer Immunol Immunother 2010; 59: 1551–1560.

    Article  CAS  Google Scholar 

  55. van der Veken LT, Hagedoorn RS, van Loenen MM, Willemze R, Falkenburg JH, Heemskerk MH . Alphabeta T-cell receptor engineered gammadelta T cells mediate effective antileukemic reactivity. Cancer Res 2006; 66: 3331–3337.

    Article  CAS  Google Scholar 

  56. van der Veken LT, Coccoris M, Swart E, Falkenburg JH, Schumacher TN, Heemskerk MH . Alpha beta T cell receptor transfer to gamma delta T cells generates functional effector cells without mixed TCR dimers in vivo. J Immunol 2009; 182: 164–170.

    Article  CAS  Google Scholar 

  57. Hiasa A, Nishikawa H, Hirayama M, Kitano S, Okamoto S, Chono H et al. Rapid alphabeta TCR-mediated responses in gammadelta T cells transduced with cancer-specific TCR genes. Gene Therapy 2009; 16: 620–628.

    Article  CAS  Google Scholar 

  58. Kruschinski A, Moosmann A, Poschke I, Norell H, Chmielewski M, Seliger B et al. Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc Natl Acad Sci USA 2008; 105: 17481–17486.

    Article  CAS  Google Scholar 

  59. Heemskerk MH, Hoogeboom M, Hagedoorn R, Kester MG, Willemze R, Falkenburg JH . Reprogramming of virus-specific T cells into leukemia-reactive T cells using T cell receptor gene transfer. J Exp Med 2004; 199: 885–894.

    Article  CAS  Google Scholar 

  60. Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H et al. Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res 2009; 69: 9003–9011.

    Article  CAS  Google Scholar 

  61. Wucherpfennig KW, Gagnon E, Call MJ, Huseby ES, Call ME . Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harb Perspect Biol 2010; 2: a005140.

    Article  Google Scholar 

  62. Bartok I, Holland SJ, Kessels HW, Silk JD, Alkhinji M, Dyson J . T cell receptor CDR3 loops influence alphabeta pairing. Mol Immunol 2010; 47: 1613–1618.

    Article  CAS  Google Scholar 

  63. Hart DP, Xue SA, Thomas S, Cesco-Gaspere M, Tranter A, Willcox B et al. Retroviral transfer of a dominant TCR prevents surface expression of a large proportion of the endogenous TCR repertoire in human T cells. Gene Therapy 2008; 15: 625–631.

    Article  CAS  Google Scholar 

  64. Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM et al. Single-chain antigen-binding proteins. Science 1988; 242: 423–426.

    Article  CAS  Google Scholar 

  65. Spiotto MT, Rowley DA, Schreiber H . Bystander elimination of antigen loss variants in established tumors. Nat Med 2004; 10: 294–298.

    Article  CAS  Google Scholar 

  66. Zhang B, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med 2007; 204: 49–55.

    Article  CAS  Google Scholar 

  67. Willemsen RA, Debets R, Hart E, Hoogenboom HR, Bolhuis RL, Chames P . A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes. Gene Therapy 2001; 8: 1601–1608.

    Article  CAS  Google Scholar 

  68. Stewart-Jones G, Wadle A, Hombach A, Shenderov E, Held G, Fischer E et al. Rational development of high-affinity T-cell receptor-like antibodies. Proc Natl Acad Sci USA 2009; 106: 5784–5788.

    Article  CAS  Google Scholar 

  69. Chames P, Willemsen RA, Rojas G, Dieckmann D, Rem L, Schuler G et al. TCR-like human antibodies expressed on human CTLs mediate antibody affinity-dependent cytolytic activity. J Immunol 2002; 169: 1110–1118.

    Article  CAS  Google Scholar 

  70. Verma B, Neethling FA, Caseltine S, Fabrizio G, Largo S, Duty JA et al. TCR mimic monoclonal antibody targets a specific peptide/HLA class I complex and significantly impedes tumor growth in vivo using breast cancer models. J Immunol 2010; 184: 2156–2165.

    Article  CAS  Google Scholar 

  71. Teague RM, Greenberg PD, Fowler C, Huang MZ, Tan X, Morimoto J et al. Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor. Immunity 2008; 28: 662–674.

    Article  CAS  Google Scholar 

  72. Cheung AF, Dupage MJ, Dong HK, Chen J, Jacks T . Regulated expression of a tumor-associated antigen reveals multiple levels of T-cell tolerance in a mouse model of lung cancer. Cancer Res 2008; 68: 9459–9468.

    Article  CAS  Google Scholar 

  73. Richman SA, Kranz DM . Display, engineering, and applications of antigen-specific T cell receptors. Biomol Eng 2007; 24: 361–373.

    Article  CAS  Google Scholar 

  74. Zhao Y, Bennett AD, Zheng Z, Wang QJ, Robbins PF, Yu LY et al. High-affinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines. J Immunol 2007; 179: 5845–5854.

    Article  CAS  Google Scholar 

  75. Chervin AS, Stone JD, Bowerman NA, Kranz DM . Cutting edge: inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands. J Immunol 2009; 183: 7639–7643.

    Article  CAS  Google Scholar 

  76. Dossett ML, Teague RM, Schmitt TM, Tan X, Cooper LJ, Pinzon C et al. Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR. Mol Ther 2009; 17: 742–749.

    Article  CAS  Google Scholar 

  77. Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008; 14: 1264–1270.

    Article  CAS  Google Scholar 

  78. Kranz DM, Tonegawa S, Eisen HN . Attachment of an anti-receptor antibody to non-target cells renders them susceptible to lysis by a clone of cytotoxic T lymphocytes. Proc Natl Acad Sci USA 1984; 81: 7922–7926.

    Article  CAS  Google Scholar 

  79. Shusta EV, Holler PD, Kieke MC, Kranz DM, Wittrup KD . Directed evolution of a stable scaffold for T-cell receptor engineering. Nat Biotechnol 2000; 18: 754–759.

    Article  CAS  Google Scholar 

  80. Haynes NM, Trapani JA, Teng MW, Jackson JT, Cerruti L, Jane SM et al. Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood 2002; 100: 3155–3163.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the staff of University of Illinois Biotechnology Center for assistance in fluorescence activated cell sorting. We also thank Phil Holler for original engineering of high-affinity TCRs, including m33, and Carolina Soto for assistance with the m33T cell cytotoxicity assays. This work was supported by Grants from the NIH, GM55767 (to DMK), CA097296 (to HS and DMK), CA033084 and CA18029 (to PDG), a grant from the James S McDonnell Foundation (to DMK), and Grant 7040 from the Leukemia and Lymphoma Society (to PDG). BE was supported by a Research Fellowship of the DFG; JDS was supported by the Samuel and Ruth Engelberg/Irvington Institute Fellowship of the Cancer Research Institute.

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Authors and Affiliations

  1. Department of Biochemistry, University of Illinois, Urbana, IL, USA

    D H Aggen, A S Chervin, J D Stone, S A Richman & D M Kranz

  2. Department of Immunology, and the Division of Clinical Research, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    T M Schmitt & P D Greenberg

  3. Department of Pathology and the Committee on Immunology, The University of Chicago, Chicago, IL, USA

    B Engels & H Schreiber

  4. Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN, USA

    K H Piepenbrink & B M Baker

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  1. D H Aggen
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  2. A S Chervin
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Aggen, D., Chervin, A., Schmitt, T. et al. Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains. Gene Ther 19, 365–374 (2012). https://doi.org/10.1038/gt.2011.104

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