Skip to main content

Use of RNA Interference with TCR Transfer to Enhance Safety and Efficiency

Part of the Methods in Molecular Biology book series (MIMB,volume 2115)

Abstract

The gene transfer of T-cell receptors (TCRs) is an attractive strategy for adoptive cell therapy, allowing the transfer of reactivity against antigens that may not otherwise engender an immune response. The TCRs recognize intracellular or extracellular antigens presented in the context of MHC class I or II, respectively. This broadens the range of targets considerably, compared to antibodies and chimeric antigen receptors, that are generally confined to surface antigens. However, TCR transfer must overcome some technical hurdles, relating to interference with endogenous α- and β-TCR chains and competition with other existing TCR infrastructure of T cells. In this review, we will outline the challenges facing TCR gene transfer and compare several approaches to address them. We will then focus upon one of the most promising amongst these—RNA interference—and detail the methods involved in designing and using this technology.

Key words

  • T cell receptor
  • TCR gene transfer
  • RNA interference
  • Small interfering RNAs
  • immunotherapy
  • Adoptive cell therapy

This is a preview of subscription content, access via your institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-0716-0290-4_18
  • Chapter length: 23 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   149.00
Price excludes VAT (USA)
  • ISBN: 978-1-0716-0290-4
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   199.99
Price excludes VAT (USA)
Hardcover Book
USD   279.99
Price excludes VAT (USA)

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Kuhns MS, Davis MM, Garcia KC (2006) Deconstructing the form and function of the TCR/CD3 complex. Immunity 24(2):133–139. https://doi.org/10.1016/j.immuni.2006.01.006

    CAS  CrossRef  PubMed  Google Scholar 

  2. Wucherpfennig KW, Gagnon E, Call MJ, Huseby ES, Call ME (2010) Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harb Perspect Biol 2(4):a005140. https://doi.org/10.1101/cshperspect.a005140

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  3. Kane LP, Lin J, Weiss A (2000) Signal transduction by the TCR for antigen. Curr Opin Immunol 12(3):242–249

    CAS  CrossRef  PubMed  Google Scholar 

  4. Artyomov MN, Lis M, Devadas S, Davis MM, Chakraborty AK (2010) CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery. Proc Natl Acad Sci U S A 107(39):16916–16921. https://doi.org/10.1073/pnas.1010568107

    CrossRef  PubMed  PubMed Central  Google Scholar 

  5. Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA (2016) CD28 costimulation: from mechanism to therapy. Immunity 44(5):973–988. https://doi.org/10.1016/j.immuni.2016.04.020

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  6. Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA (2013) Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 19(6):747–752. https://doi.org/10.1038/nm.3161

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  7. Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348(6230):69–74. https://doi.org/10.1126/science.aaa4971

    CAS  CrossRef  PubMed  Google Scholar 

  8. Parkhurst M, Gros A, Pasetto A, Prickett T, Crystal JS, Robbins P, Rosenberg SA (2017) Isolation of T-cell receptors specifically reactive with mutated tumor-associated antigens from tumor-infiltrating lymphocytes based on CD137 expression. Clin Cancer Res 23(10):2491–2505. https://doi.org/10.1158/1078-0432.CCR-16-2680

    CAS  CrossRef  PubMed  Google Scholar 

  9. Muenst S, Laubli H, Soysal SD, Zippelius A, Tzankov A, Hoeller S (2016) The immune system and cancer evasion strategies: therapeutic concepts. J Intern Med 279(6):541–562. https://doi.org/10.1111/joim.12470

    CAS  CrossRef  PubMed  Google Scholar 

  10. Fridman WH (2018) From cancer immune surveillance to cancer immunoediting: birth of modern immuno-oncology. J Immunol 201(3):825–826. https://doi.org/10.4049/jimmunol.1800827

    CAS  CrossRef  PubMed  Google Scholar 

  11. Ribatti D (2017) The concept of immune surveillance against tumors. The first theories. Oncotarget 8(4):7175–7180. https://doi.org/10.18632/oncotarget.12739

    CrossRef  PubMed  Google Scholar 

  12. Mittal D, Gubin MM, Schreiber RD, Smyth MJ (2014) New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape. Curr Opin Immunol 27:16–25. https://doi.org/10.1016/j.coi.2014.01.004

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  13. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111. https://doi.org/10.1038/35074122

    CAS  CrossRef  PubMed  Google Scholar 

  14. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA et al (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319(25):1676–1680. https://doi.org/10.1056/NEJM198812223192527

    CAS  CrossRef  PubMed  Google Scholar 

  15. Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12(4):269–281. https://doi.org/10.1038/nri3191

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  16. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298(5594):850–854. https://doi.org/10.1126/science.1076514

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  17. Yee C, Savage PA, Lee PP, Davis MM, Greenberg PD (1999) Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J Immunol 162(4):2227–2234

    CAS  PubMed  Google Scholar 

  18. Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA (2003) Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 26(4):332–342

    CrossRef  PubMed  PubMed Central  Google Scholar 

  19. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8(4):299–308. https://doi.org/10.1038/nrc2355

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  20. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188:22–32

    CAS  CrossRef  PubMed  Google Scholar 

  21. Theobald M, Biggs J, Hernandez J, Lustgarten J, Labadie C, Sherman LA (1997) Tolerance to p53 by A2.1-restricted cytotoxic T lymphocytes. J Exp Med 185(5):833–841. https://doi.org/10.1084/jem.185.5.833

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  22. Kuball J, Schuler M, Antunes Ferreira E, Herr W, Neumann M, Obenauer-Kutner L, Westreich L, Huber C, Wolfel T, Theobald M (2002) Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man. Gene Ther 9(13):833–843. https://doi.org/10.1038/sj.gt.3301709

    CAS  CrossRef  PubMed  Google Scholar 

  23. Dembic Z, Haas W, Weiss S, McCubrey J, Kiefer H, von Boehmer H, Steinmetz M (1986) Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature 320(6059):232–238

    CAS  CrossRef  PubMed  Google Scholar 

  24. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314(5796):126–129. https://doi.org/10.1126/science.1129003

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  25. Schumacher TN (2002) T-cell-receptor gene therapy. Nat Rev Immunol 2(7):512–519. https://doi.org/10.1038/nri841

    CAS  CrossRef  PubMed  Google Scholar 

  26. Eshhar Z, Waks T, Bendavid A, Schindler DG (2001) Functional expression of chimeric receptor genes in human T cells. J Immunol Methods 248(1–2):67–76

    CAS  CrossRef  PubMed  Google Scholar 

  27. Barrett DM, Grupp SA, June CH (2015) Chimeric antigen receptor- and TCR-modified T cells enter main street and wall street. J Immunol 195(3):755–761. https://doi.org/10.4049/jimmunol.1500751

    CAS  CrossRef  PubMed  Google Scholar 

  28. van Loenen MM, de Boer R, Amir AL, Hagedoorn RS, Volbeda GL, Willemze R, van Rood JJ, Falkenburg JH, Heemskerk MH (2010) Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc Natl Acad Sci U S A 107(24):10972–10977. https://doi.org/10.1073/pnas.1005802107

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  29. Bendle GM, Linnemann C, Hooijkaas AI, Bies L, de Witte MA, Jorritsma A, Kaiser AD, Pouw N, Debets R, Kieback E, Uckert W, Song JY, Haanen JB, Schumacher TN (2010) Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 16(5):565–570. https://doi.org/10.1038/nm.2128. 561 p. Following 570

    CAS  CrossRef  PubMed  Google Scholar 

  30. Cohen CJ, Zheng Z, Bray R, Zhao Y, Sherman LA, Rosenberg SA, Morgan RA (2005) Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR. J Immunol 175(9):5799–5808

    CAS  CrossRef  PubMed  Google Scholar 

  31. Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA (2006) 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 66(17):8878–8886. https://doi.org/10.1158/0008-5472.CAN-06-1450

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  32. Voss RH, Kuball J, Engel R, Guillaume P, Romero P, Huber C, Theobald M (2006) Redirection of T cells by delivering a transgenic mouse-derived MDM2 tumor antigen-specific TCR and its humanized derivative is governed by the CD8 coreceptor and affects natural human TCR expression. Immunol Res 34(1):67–87. https://doi.org/10.1385/IR:34:1:67

    CAS  CrossRef  PubMed  Google Scholar 

  33. Sommermeyer D, Uckert W (2010) Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR gene-modified T cells. J Immunol 184(11):6223–6231. https://doi.org/10.4049/jimmunol.0902055

    CAS  CrossRef  PubMed  Google Scholar 

  34. Boulter JM, Glick M, Todorov PT, Baston E, Sami M, Rizkallah P, Jakobsen BK (2003) Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng 16(9):707–711

    CAS  CrossRef  PubMed  Google Scholar 

  35. Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C, Greenberg PD (2007) Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 109(6):2331–2338. https://doi.org/10.1182/blood-2006-05-023069

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  36. Voss RH, Willemsen RA, Kuball J, Grabowski M, Engel R, Intan RS, Guillaume P, Romero P, Huber C, Theobald M (2008) Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 180(1):391–401

    CAS  CrossRef  PubMed  Google Scholar 

  37. Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin EF, Vignali DA (2004) Correction of multi-gene deficiency in vivo using a single ‘self-cleaving’ 2A peptide-based retroviral vector. Nat Biotechnol 22(5):589–594. https://doi.org/10.1038/nbt957

    CAS  CrossRef  PubMed  Google Scholar 

  38. Yang S, Cohen CJ, Peng PD, Zhao Y, Cassard L, Yu Z, Zheng Z, Jones S, Restifo NP, Rosenberg SA, Morgan RA (2008) Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition. Gene Ther 15(21):1411–1423. https://doi.org/10.1038/gt.2008.90

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  39. Scholten KB, Kramer D, Kueter EW, Graf M, Schoedl T, Meijer CJ, Schreurs MW, Hooijberg E (2006) Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin Immunol 119(2):135–145. https://doi.org/10.1016/j.clim.2005.12.009

    CAS  CrossRef  PubMed  Google Scholar 

  40. Willcox BE, Gao GF, Wyer JR, O’Callaghan CA, Boulter JM, Jones EY, van der Merwe PA, Bell JI, Jakobsen BK (1999) Production of soluble alphabeta T-cell receptor heterodimers suitable for biophysical analysis of ligand binding. Protein Sci 8(11):2418–2423. https://doi.org/10.1110/ps.8.11.2418

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  41. Foley KC, Spear TT, Murray DC, Nagato K, Garrett-Mayer E, Nishimura MI (2017) HCV T cell receptor chain modifications to enhance expression, pairing, and antigen recognition in T cells for adoptive transfer. Mol Ther Oncolytics 5:105–115. https://doi.org/10.1016/j.omto.2017.05.004

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  42. Bethune MT, Gee MH, Bunse M, Lee MS, Gschweng EH, Pagadala MS, Zhou J, Cheng D, Heath JR, Kohn DB, Kuhns MS, Uckert W, Baltimore D (2016) Domain-swapped T cell receptors improve the safety of TCR gene therapy. elife 5. https://doi.org/10.7554/eLife.19095

  43. Cohen CJ, Li YF, El-Gamil M, Robbins PF, Rosenberg SA, Morgan RA (2007) Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 67(8):3898–3903. https://doi.org/10.1158/0008-5472.CAN-06-3986

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  44. Hart DP, Xue SA, Thomas S, Cesco-Gaspere M, Tranter A, Willcox B, Lee SP, Steven N, Morris EC, Stauss HJ (2008) Retroviral transfer of a dominant TCR prevents surface expression of a large proportion of the endogenous TCR repertoire in human T cells. Gene Ther 15(8):625–631. https://doi.org/10.1038/sj.gt.3303078

    CAS  CrossRef  PubMed  Google Scholar 

  45. Reus K, Mayer J, Sauter M, Zischler H, Muller-Lantzsch N, Meese E (2001) HERV-K(OLD): ancestor sequences of the human endogenous retrovirus family HERV-K(HML-2). J Virol 75(19):8917–8926. https://doi.org/10.1128/JVI.75.19.8917-8926.2001

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  46. Reuss S, Sebestyen Z, Heinz N, Loew R, Baum C, Debets R, Uckert W (2014) TCR-engineered T cells: a model of inducible TCR expression to dissect the interrelationship between two TCRs. Eur J Immunol 44(1):265–274. https://doi.org/10.1002/eji.201343591

    CAS  CrossRef  PubMed  Google Scholar 

  47. Willemsen RA, Weijtens ME, Ronteltap C, Eshhar Z, Gratama JW, Chames P, Bolhuis RL (2000) Grafting primary human T lymphocytes with cancer-specific chimeric single chain and two chain TCR. Gene Ther 7(16):1369–1377. https://doi.org/10.1038/sj.gt.3301253

    CAS  CrossRef  PubMed  Google Scholar 

  48. Chung S, Wucherpfennig KW, Friedman SM, Hafler DA, Strominger JL (1994) Functional three-domain single-chain T-cell receptors. Proc Natl Acad Sci U S A 91(26):12654–12658

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  49. Voss RH, Thomas S, Pfirschke C, Hauptrock B, Klobuch S, Kuball J, Grabowski M, Engel R, Guillaume P, Romero P, Huber C, Beckhove P, Theobald M (2010) Coexpression of the T-cell receptor constant alpha domain triggers tumor reactivity of single-chain TCR-transduced human T cells. Blood 115(25):5154–5163. https://doi.org/10.1182/blood-2009-11-254078

    CAS  CrossRef  PubMed  Google Scholar 

  50. Knies D, Klobuch S, Xue SA, Birtel M, Echchannaoui H, Yildiz O, Omokoko T, Guillaume P, Romero P, Stauss H, Sahin U, Herr W, Theobald M, Thomas S, Voss RH (2016) An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells. Oncotarget 7(16):21199–21221. https://doi.org/10.18632/oncotarget.8385

    CrossRef  PubMed  PubMed Central  Google Scholar 

  51. Ahmadi M, King JW, Xue SA, Voisine C, Holler A, Wright GP, Waxman J, Morris E, Stauss HJ (2011) CD3 limits the efficacy of TCR gene therapy in vivo. Blood 118(13):3528–3537. https://doi.org/10.1182/blood-2011-04-346338

    CAS  CrossRef  PubMed  Google Scholar 

  52. Govers C, Sebestyen Z, Roszik J, van Brakel M, Berrevoets C, Szoor A, Panoutsopoulou K, Broertjes M, Van T, Vereb G, Szollosi J, Debets R (2014) TCRs genetically linked to CD28 and CD3epsilon do not mispair with endogenous TCR chains and mediate enhanced T cell persistence and anti-melanoma activity. J Immunol 193(10):5315–5326. https://doi.org/10.4049/jimmunol.1302074

    CAS  CrossRef  PubMed  Google Scholar 

  53. Walseng E, Koksal H, Sektioglu IM, Fane A, Skorstad G, Kvalheim G, Gaudernack G, Inderberg EM, Walchli S (2017) A TCR-based chimeric antigen receptor. Sci Rep 7(1):10713. https://doi.org/10.1038/s41598-017-11126-y

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  54. Walseng E, Walchli S, Fallang LE, Yang W, Vefferstad A, Areffard A, Olweus J (2015) Soluble T-cell receptors produced in human cells for targeted delivery. PLoS One 10(4):e0119559. https://doi.org/10.1371/journal.pone.0119559

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  55. Liddy N, Bossi G, Adams KJ, Lissina A, Mahon TM, Hassan NJ, Gavarret J, Bianchi FC, Pumphrey NJ, Ladell K, Gostick E, Sewell AK, Lissin NM, Harwood NE, Molloy PE, Li Y, Cameron BJ, Sami M, Baston EE, Todorov PT, Paston SJ, Dennis RE, Harper JV, Dunn SM, Ashfield R, Johnson A, McGrath Y, Plesa G, June CH, Kalos M, Price DA, Vuidepot A, Williams DD, Sutton DH, Jakobsen BK (2012) Monoclonal TCR-redirected tumor cell killing. Nat Med 18(6):980–987. https://doi.org/10.1038/nm.2764

    CAS  CrossRef  PubMed  Google Scholar 

  56. Baeuerle PA, Kufer P, Bargou R (2009) BiTE: teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther 11(1):22–30

    CAS  PubMed  Google Scholar 

  57. Oates J, Jakobsen BK (2013) ImmTACs: novel bi-specific agents for targeted cancer therapy. Oncoimmunology 2(2):e22891. https://doi.org/10.4161/onci.22891

    CrossRef  PubMed  PubMed Central  Google Scholar 

  58. Poirot L, Philip B, Schiffer-Mannioui C, Le Clerre D, Chion-Sotinel I, Derniame S, Potrel P, Bas C, Lemaire L, Galetto R, Lebuhotel C, Eyquem J, Cheung GW, Duclert A, Gouble A, Arnould S, Peggs K, Pule M, Scharenberg AM, Smith J (2015) Multiplex genome-edited T-cell manufacturing platform for “off-the-shelf” adoptive t-cell immunotherapies. Cancer Res 75(18):3853–3864. https://doi.org/10.1158/0008-5472.CAN-14-3321

    CAS  CrossRef  PubMed  Google Scholar 

  59. Osborn MJ, Webber BR, Knipping F, Lonetree CL, Tennis N, DeFeo AP, McElroy AN, Starker CG, Lee C, Merkel S, Lund TC, Kelly-Spratt KS, Jensen MC, Voytas DF, von Kalle C, Schmidt M, Gabriel R, Hippen KL, Miller JS, Scharenberg AM, Tolar J, Blazar BR (2016) Evaluation of TCR gene editing achieved by TALENs, CRISPR/Cas9, and megaTAL nucleases. Mol Ther 24(3):570–581. https://doi.org/10.1038/mt.2015.197

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  60. Mensali N, Dillard P, Hebeisen M, Lorenz S, Theodossiou T, Myhre MR, Fane A, Gaudernack G, Kvalheim G, Myklebust JH, Inderberg EM, Walchli S (2019) NK cells specifically TCR-dressed to kill cancer cells. EBioMedicine 40:106–117. https://doi.org/10.1016/j.ebiom.2019.01.031

    CrossRef  PubMed  PubMed Central  Google Scholar 

  61. Legut M, Dolton G, Mian AA, Ottmann OG, Sewell AK (2018) CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells. Blood 131(3):311–322. https://doi.org/10.1182/blood-2017-05-787598

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  62. Certo MT, Gwiazda KS, Kuhar R, Sather B, Curinga G, Mandt T, Brault M, Lambert AR, Baxter SK, Jacoby K, Ryu BY, Kiem HP, Gouble A, Paques F, Rawlings DJ, Scharenberg AM (2012) Coupling endonucleases with DNA end-processing enzymes to drive gene disruption. Nat Methods 9(10):973–975. https://doi.org/10.1038/nmeth.2177

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  63. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ, Reik A, Chu V, Paschon DE, Zhang L, Kuball J, Camisa B, Bondanza A, Casorati G, Ponzoni M, Ciceri F, Bordignon C, Greenberg PD, Holmes MC, Gregory PD, Naldini L, Bonini C (2012) Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 18(5):807–815. https://doi.org/10.1038/nm.2700

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  64. Berdien B, Mock U, Atanackovic D, Fehse B (2014) TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. Gene Ther 21(6):539–548. https://doi.org/10.1038/gt.2014.26

    CAS  CrossRef  PubMed  Google Scholar 

  65. Georgiadis C, Preece R, Nickolay L, Etuk A, Petrova A, Ladon D, Danyi A, Humphryes-Kirilov N, Ajetunmobi A, Kim D, Kim JS, Qasim W (2018) Long terminal repeat CRISPR-CAR-coupled “universal” T cells mediate potent anti-leukemic effects. Mol Ther 26(5):1215–1227. https://doi.org/10.1016/j.ymthe.2018.02.025

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  66. Roth TL, Puig-Saus C, Yu R, Shifrut E, Carnevale J, Li PJ, Hiatt J, Saco J, Krystofinski P, Li H, Tobin V, Nguyen DN, Lee MR, Putnam AL, Ferris AL, Chen JW, Schickel JN, Pellerin L, Carmody D, Alkorta-Aranburu G, Del Gaudio D, Matsumoto H, Morell M, Mao Y, Cho M, Quadros RM, Gurumurthy CB, Smith B, Haugwitz M, Hughes SH, Weissman JS, Schumann K, Esensten JH, May AP, Ashworth A, Kupfer GM, Greeley SAW, Bacchetta R, Meffre E, Roncarolo MG, Romberg N, Herold KC, Ribas A, Leonetti MD, Marson A (2018) Reprogramming human T cell function and specificity with non-viral genome targeting. Nature 559(7714):405–409. https://doi.org/10.1038/s41586-018-0326-5

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  67. Albers JJ, Ammon T, Gosmann D, Audehm S, Thoene S, Winter C, Secci R, Wolf A, Stelzl A, Steiger K, Ruland J, Bassermann F, Kupatt C, Anton M, Krackhardt AM (2019) Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejection. Life Sci Alliance 2(2). https://doi.org/10.26508/lsa.201900367

    CrossRef  PubMed  PubMed Central  Google Scholar 

  68. Davis L, Maizels N (2014) Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair. Proc Natl Acad Sci U S A 111(10):E924–E932. https://doi.org/10.1073/pnas.1400236111

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  69. Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK (2016) High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529(7587):490–495. https://doi.org/10.1038/nature16526

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  70. Chen JS, Dagdas YS, Kleinstiver BP, Welch MM, Sousa AA, Harrington LB, Sternberg SH, Joung JK, Yildiz A, Doudna JA (2017) Enhanced proofreading governs CRISPR–Cas9 targeting accuracy. Nature. https://doi.org/10.1038/nature24268

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  71. Kosicki M, Tomberg K, Bradley A (2018) Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. https://doi.org/10.1038/nbt.4192

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  72. Rezza A, Jacquet C, Le Pillouer A, Lafarguette F, Ruptier C, Billandon M, Isnard Petit P, Trouttet S, Thiam K, Fraichard A, Cherifi Y (2019) Unexpected genomic rearrangements at targeted loci associated with CRISPR/Cas9-mediated knock-in. Sci Rep 9(1):3486. https://doi.org/10.1038/s41598-019-40181-w

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  73. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811. https://doi.org/10.1038/35888

    CAS  CrossRef  PubMed  Google Scholar 

  74. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498. https://doi.org/10.1038/35078107

    CAS  CrossRef  PubMed  Google Scholar 

  75. Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS (2002) Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 16(8):948–958. https://doi.org/10.1101/gad.981002

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  76. Rao DD, Senzer N, Cleary MA, Nemunaitis J (2009) Comparative assessment of siRNA and shRNA off target effects: what is slowing clinical development. Cancer Gene Ther 16(11):807–809. https://doi.org/10.1038/cgt.2009.53

    CAS  CrossRef  PubMed  Google Scholar 

  77. Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I (2009) Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res 69(23):9003–9011

    CAS  CrossRef  PubMed  Google Scholar 

  78. Bunse M, Bendle GM, Linnemann C, Bies L, Schulz S, Schumacher TN, Uckert W (2014) RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR dimers following TCR gene transfer. Mol Ther 22(11):1983–1991. https://doi.org/10.1038/mt.2014.142

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  79. Campillo-Davo D, Fujiki F, Van den Bergh JMJ, De Reu H, Smits E, Goossens H, Sugiyama H, Lion E, Berneman ZN, Van Tendeloo V (2018) Efficient and non-genotoxic RNA-based engineering of human T cells using tumor-specific T cell receptors with minimal TCR mispairing. Front Immunol 9:2503. https://doi.org/10.3389/fimmu.2018.02503

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  80. Tawara I, Kageyama S, Miyahara Y, Fujiwara H, Nishida T, Akatsuka Y, Ikeda H, Tanimoto K, Terakura S, Murata M, Inaguma Y, Masuya M, Inoue N, Kidokoro T, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Naoe T, Emi N, Yasukawa M, Katayama N, Shiku H (2017) Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS. Blood 130(18):1985–1994. https://doi.org/10.1182/blood-2017-06-791202

    CAS  CrossRef  PubMed  Google Scholar 

  81. Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H (2015) Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer. Clin Cancer Res 21(10):2268–2277. https://doi.org/10.1158/1078-0432.CCR-14-1559

    CAS  CrossRef  PubMed  Google Scholar 

  82. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, de Saint BG, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, Le Deist F, Fischer A, Cavazzana-Calvo M (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302(5644):415–419. https://doi.org/10.1126/science.1088547

    CAS  CrossRef  PubMed  Google Scholar 

  83. Yoshida J, Akagi K, Misawa R, Kokubu C, Takeda J, Horie K (2017) Chromatin states shape insertion profiles of the piggyBac, Tol2 and Sleeping Beauty transposons and murine leukemia virus. Sci Rep 7:43613. https://doi.org/10.1038/srep43613

    CrossRef  PubMed  PubMed Central  Google Scholar 

  84. Clauss J, Obenaus M, Miskey C, Ivics Z, Izsvak Z, Uckert W, Bunse M (2018) Efficient non-viral T-cell engineering by sleeping beauty minicircles diminishing DNA toxicity and miRNAs silencing the endogenous T-cell receptors. Hum Gene Ther 29(5):569–584. https://doi.org/10.1089/hum.2017.136

    CAS  CrossRef  PubMed  Google Scholar 

  85. Newrzela S, Cornils K, Li Z, Baum C, Brugman MH, Hartmann M, Meyer J, Hartmann S, Hansmann ML, Fehse B, von Laer D (2008) Resistance of mature T cells to oncogene transformation. Blood 112(6):2278–2286. https://doi.org/10.1182/blood-2007-12-128751

    CAS  CrossRef  PubMed  Google Scholar 

  86. Marcucci KT, Jadlowsky JK, Hwang WT, Suhoski-Davis M, Gonzalez VE, Kulikovskaya I, Gupta M, Lacey SF, Plesa G, Chew A, Melenhorst JJ, Levine BL, June CH (2018) Retroviral and lentiviral safety analysis of gene-modified T cell products and infused HIV and oncology patients. Mol Ther 26(1):269–279. https://doi.org/10.1016/j.ymthe.2017.10.012

    CAS  CrossRef  PubMed  Google Scholar 

  87. Ni B (2017) First-ever CAR T-cell therapy approved in U.S. Cancer Discov 7(10):OF1. https://doi.org/10.1158/2159-8290.CD-NB2017-126

    CrossRef  Google Scholar 

  88. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, Litzky L, Bagg A, Carreno BM, Cimino PJ, Binder-Scholl GK, Smethurst DP, Gerry AB, Pumphrey NJ, Bennett AD, Brewer JE, Dukes J, Harper J, Tayton-Martin HK, Jakobsen BK, Hassan NJ, Kalos M, June CH (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122(6):863–871. https://doi.org/10.1182/blood-2013-03-490565

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  89. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36(2):133–151. https://doi.org/10.1097/CJI.0b013e3182829903

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  90. Almasbak H, Walseng E, Kristian A, Myhre MR, Suso EM, Munthe LA, Andersen JT, Wang MY, Kvalheim G, Gaudernack G, Kyte JA (2015) Inclusion of an IgG1-Fc spacer abrogates efficacy of CD19 CAR T cells in a xenograft mouse model. Gene Ther 22(5):391–403. https://doi.org/10.1038/gt.2015.4

    CAS  CrossRef  PubMed  Google Scholar 

  91. Kyte JA, Fane A, Pule M, Gaudernack G (2019) Transient redirection of T cells for adoptive cell therapy with telomerase-specific T helper cell receptors isolated from long term survivors after cancer vaccination. Oncoimmunology 8(4):e1565236. https://doi.org/10.1080/2162402X.2019.1565236

    CrossRef  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicholas Paul Casey .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Verify currency and authenticity via CrossMark

Cite this protocol

Casey, N.P., Kyte, J.A., Fujiwara, H. (2020). Use of RNA Interference with TCR Transfer to Enhance Safety and Efficiency. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0290-4_18

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0289-8

  • Online ISBN: 978-1-0716-0290-4

  • eBook Packages: Springer Protocols