Skip to main content

Genome Engineering Tools in Immunotherapy

  • Chapter
  • First Online:
Systems and Synthetic Immunology

Abstract

Immunotherapy is a breakthrough in the potential treatment of cancer as well as preventing future relapses by stimulating the immune system in the recognition and killing of cancer cells. Numerous strategies are ongoing in the clinical laboratories for the advancements in the immunotherapy approaches which include therapeutic engineered T lymphocytes, vector-based (noncellular) cancer vaccines, dendritic cell vaccines, and immune checkpoint blockade. Regardless of their capacity, continuous research is required to recognize the failures of cancer response toward strong immunotherapy treatment as well as to envisage the therapeutic combinatorial strategies appropriate for patient-specific ways. Fundamental to these challenges underlie the technological methods for rapid and thorough characterization of tumors-immune microenvironments, immune response monitoring of patients, predictive tools to screen potential and sensitive therapies, tumor regression, and tumor dissemination throughout and after the therapy. The emerging field of immune engineering addresses these challenges and contributed the tools and approaches to facilitate the clinical transformation of immunotherapy. Customized and programmable site-specific nucleases have already revolutionized our ability to interrogate genomic functions and introduce genetic manipulations in diseases which are intractable with traditional therapies for potential clinical applications. In this chapter, we highlight the developments, recent technological advances, and applications of these tools in the diagnosis, treatment, and cancer monitoring, as well as the ongoing challenges in their uses as a platform technology in the context of immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Capecchi MR (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6(6):507–512. https://doi.org/10.1038/nrg1619

    Article  CAS  PubMed  Google Scholar 

  2. Saha SK, Saikot FK, Rahman MS, Jamal MAHM, Rahman SMK, Islam SMR, Kim KH (2019) Programmable molecular scissors: applications of a new tool for genome editing in biotech. Mol Ther Nucleic Acids 14:212–238. https://doi.org/10.1016/j.omtn.2018.11.016

    Article  CAS  PubMed  Google Scholar 

  3. Maeder ML, Gersbach CA (2016) Genome-editing technologies for gene and cell therapy. Mol Ther 24(3):430–446. https://doi.org/10.1038/mt.2016.10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chari R, Church GM (2017) Beyond editing to writing large genomes. Nat Rev Genet 18(12):749–760. https://doi.org/10.1038/nrg.2017.59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rouet P, Smih F, Jasin M (1994) Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc Natl Acad Sci U S A 91(13):6064–6068

    Article  CAS  Google Scholar 

  6. Ceccaldi R, Rondinelli B, D’Andrea AD (2016) Repair pathway choices and consequences at the double-strand break. Trends Cell Biol 26(1):52–64. https://doi.org/10.1016/j.tcb.2015.07.009

    Article  CAS  PubMed  Google Scholar 

  7. McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3(10):737–747. https://doi.org/10.1038/nrg908

    Article  CAS  PubMed  Google Scholar 

  8. Carroll D (2011) Genome engineering with zinc-finger nucleases. Genetics 188(4):773–782. https://doi.org/10.1534/genetics.111.131433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11(9):636–646. https://doi.org/10.1038/nrg2842

    Article  CAS  PubMed  Google Scholar 

  10. Wyman C, Kanaar R (2006) DNA double-strand break repair: All’s well that ends well. Annu Rev Genet 40:363–383. https://doi.org/10.1146/annurev.genet.40.110405.090451

    Article  CAS  PubMed  Google Scholar 

  11. Hicks WM, Yamaguchi M, Haber JE (2011) Real-time analysis of double-strand DNA break repair by homologous recombination. Proc Natl Acad Sci 108(8):3108–3115. https://doi.org/10.1073/pnas.1019660108

    Article  PubMed  Google Scholar 

  12. Povirk LF (2012) Processing of damaged DNA ends for double-strand break repair in mammalian cells. ISRN Mol Biol. https://doi.org/10.5402/2012/345805

  13. Moehle EA, Rock JM, Lee Y-L, Jouvenot Y, DeKelver RC, Gregory PD, Urnov FD, Holmes MC (2007) Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci 104(9):3055–3060. https://doi.org/10.1073/pnas.0611478104

    Article  CAS  PubMed  Google Scholar 

  14. Orlando SJ, Santiago Y, DeKelver RC, Freyvert Y, Boydston EA, Moehle EA, Choi VM, Gopalan SM, Lou JF, Li J et al (2010) Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology. Nucleic Acids Res 38(15):e152. https://doi.org/10.1093/nar/gkq512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen F, Pruett-Miller SM, Huang Y, Gjoka M, Duda K, Taunton J, Collingwood TN, Frodin M, Davis GD (2011) High-frequency genome editing using ss DNA oligonucleotides with zinc-finger nucleases. Nat Methods 8(9):753–755. https://doi.org/10.1038/nmeth.1653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Santiago Y, Chan E, Liu P-Q, Orlando S, Zhang L, Urnov FD, Holmes MC, Guschin D, Waite A, Miller JC et al (2008) Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc Natl Acad Sci 105(15):5809–5814. https://doi.org/10.1073/pnas.0800940105

    Article  PubMed  Google Scholar 

  17. Lee HJ, Kim E, Kim JS (2010) Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res 20(1):81–89. https://doi.org/10.1101/gr.099747.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brunet E, Simsek D, Tomishima M, DeKelver R, Choi VM, Gregory P, Urnov F, Weinstock DM, Jasin M (2009) Chromosomal translocations induced at specified loci in human stem cells. Proc Natl Acad Sci 106(26):10620–10625. https://doi.org/10.1073/pnas.0902076106

    Article  PubMed  Google Scholar 

  19. Lee HJ, Kweon J, Kim E, Kim S, Kim JS (2012) Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases. Genome Res 22(3):539–548. https://doi.org/10.1101/gr.129635.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Maresca M, Lin VG, Guo N, Yang Y (2013) Obligate ligation-gated recombination (ObLiGaRe): custom-designed nuclease-mediated targeted integration through nonhomologous end joining. Genome Res 23(3):539–546. https://doi.org/10.1101/gr.145441.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, Dekelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B et al (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27(9):851–857. https://doi.org/10.1038/nbt.1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29(8):731–734. https://doi.org/10.1038/nbt.1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gutschner T, Baas M, Diederichs S (2011) Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases. Genome Res 21(11):1944–1954. https://doi.org/10.1101/gr.122358.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489(7414):109–113. https://doi.org/10.1038/nature11279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Beerli RR, Barbas CF (2002) Engineering polydactyl zinc-finger transcription factors. Nat Biotechnol 20(2):135–141. https://doi.org/10.1038/nbt0202-135

    Article  CAS  PubMed  Google Scholar 

  26. Miller J, McLachlan AD, Klug A (1985) Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J 4:1609–1614

    Article  CAS  Google Scholar 

  27. Wolfe SA, Nekludova L, Pabo CO (2000) DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct 25(1):22–29

    Google Scholar 

  28. Liu Q, Segal DJ, Ghiara JB, Barbas CF (2002) Design of polydactyl zinc-finger proteins for unique addressing within complex genomes. Proc Natl Acad Sci 94:5525. https://doi.org/10.1073/pnas.94.11.5525

    Article  Google Scholar 

  29. Beerli RR, Segal DJ, Dreier B, Barbas CF III, Barbas CF (1998) Toward controlling gene expression at will: specific regulation of the erbB-2/HER-2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks. Proc Natl Acad Sci U S A 95(25):14628–14633

    Article  CAS  Google Scholar 

  30. Beerli RR, Dreier B, Barbas CF (2002) Positive and negative regulation of endogenous genes by designed transcription factors. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.040552697

  31. Segal DJ, Beerli RR, Blancafort P, Dreier B, Effertz K, Huber A, Koksch B, Lund CV, Magnenat L, Valente D et al (2003) Evaluation of a modular strategy for the construction of novel polydactyl zinc finger DNA-binding proteins. Biochemistry 42(7):2137–2148. https://doi.org/10.1021/bi026806o

    Article  CAS  PubMed  Google Scholar 

  32. Pavletich NP, Pabo CO (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 Å. Science (80-. ) 252(5007):809–817. https://doi.org/10.1126/science.2028256

    Article  CAS  Google Scholar 

  33. Segal DJ, Dreier B, Beerli RR, Barbas CF (2002) Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5’-GNN-3’ DNA target sequences. Proc Natl Acad Sci 96(6):2758–2763. https://doi.org/10.1073/pnas.96.6.2758

    Article  Google Scholar 

  34. Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA et al (2008) Rapid ‘open-source’ engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31(2):294–301. https://doi.org/10.1016/j.molcel.2008.06.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vanamee ÉS, Santagata S, Aggarwal AK (2001) FokI requires two specific DNA sites for cleavage. J Mol Biol 309(1):69–78. https://doi.org/10.1006/jmbi.2001.4635

    Article  CAS  PubMed  Google Scholar 

  36. Miller JC, Holmes MC, Wang J, Guschin DY, Lee Y-L, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA et al (2007) An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25(7):778–785. https://doi.org/10.1038/nbt1319

    Article  CAS  PubMed  Google Scholar 

  37. Szczepek M, Brondani V, Büchel J, Serrano L, Segal DJ, Cathomen T (2007) Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 25(7):786–793. https://doi.org/10.1038/nbt1317

    Article  CAS  PubMed  Google Scholar 

  38. Guo J, Gaj T, Barbas CF (2010) Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases. J Mol Biol 400(1):96–107. https://doi.org/10.1016/j.jmb.2010.04.060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beumer KJ, Trautman JK, Bozas A, Liu J-L, Rutter J, Gall JG, Carroll D (2008) Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases. Proc Natl Acad Sci 105(50):19821–19826. https://doi.org/10.1073/pnas.0810475105

    Article  PubMed  Google Scholar 

  40. Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ et al (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat. Biotechnol 26(6):702–708

    Article  CAS  Google Scholar 

  41. Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26(6):695–701. https://doi.org/10.1038/nbt1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X et al (2009) Knockout rats via embryo microinjection of zinc-finger nucleases. Science (80-. ) 325(5939):433. https://doi.org/10.1126/science.1172447

    Article  CAS  Google Scholar 

  43. Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa T (2010) Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. PLoS One 5(1):e8870. https://doi.org/10.1371/journal.pone.0008870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Osakabe K, Osakabe Y, Toki S (2010) Site-directed mutagenesis in Arabidopsis using custom-designed zinc finger nucleases. Proc Natl Acad Sci 107(26):12034–12039. https://doi.org/10.1073/pnas.1000234107

    Article  PubMed  Google Scholar 

  45. Cost GJ, Freyvert Y, Vafiadis A, Santiago Y, Miller JC, Rebar E, Collingwood TN, Snowden A, Gregory PD (2010) BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. Biotechnol Bioeng 105(2):330–340. https://doi.org/10.1002/bit.22541

    Article  CAS  PubMed  Google Scholar 

  46. Liu PQ, Chan EM, Cost GJ, Zhang L, Wang J, Miller JC, Guschin DY, Reik A, Holmes MC, Mott JE et al (2010) Generation of a triple-gene knockout mammalian cell line using engineered zinc-finger nucleases. Biotechnol Bioeng 106(1):97–105. https://doi.org/10.1002/bit.22654

    Article  CAS  PubMed  Google Scholar 

  47. Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, Schmidt C, Baller JA, Somia NV, Bogdanove AJ, Voytas DF (2011) Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 39(12):e82. https://doi.org/10.1093/nar/gkr218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Reyon D, Tsai SQ, Khgayter C, Foden JA, Sander JD, Joung JK (2012) FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30(5):460–465. https://doi.org/10.1038/nbt.2170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Briggs AW, Rios X, Chari R, Yang L, Zhang F, Mali P, Church GM (2012) Iterative capped assembly: rapid and scalable synthesis of repeat-module DNA such as TAL effectors from individual monomers. Nucleic Acids Res 40(15):e117. https://doi.org/10.1093/nar/gks624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schmid-Burgk JL, Schmidt T, Kaiser V, Höning K, Hornung V (2013) A ligation-independent cloning technique for high-throughput assembly of transcription activator-like effector genes. Nat Biotechnol 31(1):76–81. https://doi.org/10.1038/nbt.2460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kim Y, Kweon J, Kim A, Chon JK, Yoo JY, Kim HJ, Kim S, Lee C, Jeong E, Chung E et al (2013) A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 31(3):251–258. https://doi.org/10.1038/nbt.2517

    Article  CAS  PubMed  Google Scholar 

  52. Gaj T, Guo J, Kato Y, Sirk SJ, Barbas CF (2012) Targeted gene knockout by direct delivery of zinc-finger nuclease proteins. Nat Methods 9(8):805–807. https://doi.org/10.1038/nmeth.2030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakatura A (1987) Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isoenzyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 169(12):5429–5433

    Article  CAS  Google Scholar 

  54. Mojica FJM, Díez-Villaseñor C, Soria E, Juez G (2000) Biological significance of a family of regularly spaced repeats in the genomes of archaea, bacteria and mitochondria. Mol Microbiol 36(1):244–246. https://doi.org/10.1046/j.1365-2958.2000.01838.x

    Article  CAS  PubMed  Google Scholar 

  55. Jansen R, Van Embden JDA, Gaastra W, Schouls LM (2002) Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43:1565–1575. https://doi.org/10.1046/j.1365-2958.2002.02839.x

    Article  CAS  PubMed  Google Scholar 

  56. Barrangou R, van der Oost J (2013) CRISPR-Cas Systems: RNA-mediated adaptive immunity in bacteria and archaea. Springer, Berlin/Heidelberg

    Book  Google Scholar 

  57. Barrangou R, Marraffini LA (2014) CRISPR-cas systems: prokaryotes upgrade to adaptive immunity. Mol Cell. https://doi.org/10.1016/j.molcel.2014.03.011

  58. Tang T-H, Bachellerie J-P, Rozhdestvensky T, Bortolin M-L, Huber H, Drungowski M, Elge T, Brosius J, Huttenhofer A (2002) Identification of 86 candidates for small non-messenger RNAs from the archaeon Archaeoglobus fulgidus. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.112047299

  59. Haft DH, Selengut J, Mongodin EF, Nelson KE (2005) A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/cas subtypes exist in prokaryotic genomes. PLoS Comput Biol. https://doi.org/10.1371/journal.pcbi.0010060

  60. Makarova KS, Aravind L, Wolf YI, Koonin EV (2011) Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol Direct. https://doi.org/10.1186/1745-6150-6-38

  61. Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, Dickman MJ, Makarova KS, Koonin EV, Van Der Oost J (1993) Small Crispr Rnas guide antiviral defense in prokaryotes. Cancer Epidemiol Biomarkers Prev

    Google Scholar 

  62. Hale CR, Zhao P, Olson S, Duff MO, Graveley BR, Wells L, Terns RM, Terns MP (2009) RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex. Cell. https://doi.org/10.1016/j.cell.2009.07.040

  63. Mojica FJM, Díez-Villaseñor C, García-Martínez J, Soria E (2005) Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol. https://doi.org/10.1007/s00239-004-0046-3

  64. Pourcel C, Salvignol G, Vergnaud G (2005) CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology. https://doi.org/10.1099/mic.0.27437-0

  65. Bolotin A, Quinquis B, Sorokin A, Dusko Ehrlich S (2005) Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology. https://doi.org/10.1099/mic.0.28048-0

  66. Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV (2006) A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct. https://doi.org/10.1186/1745-6150-1-7

  67. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature. https://doi.org/10.1038/nature09886

  68. Garneau JE, Dupuis M-È, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH, Moineau S (2010) The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. https://doi.org/10.1038/nature09523

  69. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (80-. ). https://doi.org/10.1126/science.1225829

  70. Gasiunas G, Barrangou R, Horvath P, Siksnys V (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.1208507109

  71. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. https://doi.org/10.1038/nbt.2842

  72. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science (80-. ). https://doi.org/10.1126/science.1231143

  73. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013) RNA-guided human genome engineering via Cas9. Science (80-. ). https://doi.org/10.1126/science.1232033

  74. Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol. https://doi.org/10.1038/nbt.2507

  75. Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O et al (2013) DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. https://doi.org/10.1038/nbt.2647

  76. Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, Ishitani R, Zhang F, Nureki O (2014) Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell. https://doi.org/10.1016/j.cell.2014.02.001

  77. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/cas-mediated genome engineering. Cell. https://doi.org/10.1016/j.cell.2013.04.025

  78. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG et al (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science (80-. ). https://doi.org/10.1126/science.1247005

  79. Barrangou R, Doudna JA (2016) Applications of CRISPR technologies in research and beyond. Nat Biotechnol. https://doi.org/10.1038/nbt.3659

  80. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F et al (2012) Landscape of transcription in human cells. Nature. https://doi.org/10.1038/nature11233

  81. Zhu S, Li W, Liu J, Chen CH, Liao Q, Xu P, Xu H, Xiao T, Cao Z, Peng J et al (2016) Genome-scale deletion screening of human long non-coding RNAs using a paired-guide RNA CRISPR-Cas9 library. Nat Biotechnol. https://doi.org/10.1038/nbt.3715

  82. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA (2013) Repurposing CRISPR as an RNA-γuided platform for sequence-specific control of gene expression. Cell. https://doi.org/10.1016/j.cell.2013.02.022

  83. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC et al (2014) Genome-scale CRISPR-mediated control of gene repression and activation. Cell. https://doi.org/10.1016/j.cell.2014.09.029

  84. Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H et al (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. https://doi.org/10.1038/nature14136

  85. Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD (2014) A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell. https://doi.org/10.1016/j.cell.2014.09.039

  86. Delorme EJ, Alexander P (1964) Treatment of primary FIBROSARCOMA in the rat with immune lymphocytes. Lancet. https://doi.org/10.1016/S0140-6736(64)90126-6

  87. Morgan DA, Ruscetti FW, Gallo R (1976) Selective in vitro growth of T lymphocytes from normal human bone marrows. Science (80-. ). https://doi.org/10.1126/science.181845

  88. Eberlein TJ, Rosenstein M, Rosenberg SA (1982) Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med

    Google Scholar 

  89. Rosenberg SA, Mulé JJ, Spiess PJ, Reichert CM, Schwarz SL (1985) Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med

    Google Scholar 

  90. Donohue JH, Rosenstein M, Chang AE, Lotze MT, Robb RJ, Rosenberg SA (1984) The systemic administration of purified interleukin 2 enhances the ability of sensitized murine lymphocytes to cure a disseminated syngeneic lymphoma. J Immunol

    Google Scholar 

  91. Berendt MJ, North RJ (1980) T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med

    Google Scholar 

  92. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT et al (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492

    Article  CAS  Google Scholar 

  93. Dudley ME, Gross CA, Somerville RPT, Hong Y, Schaub NP, Rosati SF, White DE, Nathan D, Restifo NP, Steinberg SM et al (2013) Randomized selection design trial evaluating CD8 + −enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol. https://doi.org/10.1200/JCO.2012.46.6441

  94. Khammari A, Knol A-C, Nguyen J-M, Bossard C, Denis M-G, Pandolfino M-C, Quéreux G, Bercegeay S, Dréno B (2014) Adoptive TIL transfer in the adjuvant setting for melanoma: long-term patient survival. J Immunol Res. https://doi.org/10.1155/2014/186212

  95. Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science (80-. ). https://doi.org/10.1126/science.3489291

  96. Muul LM, Spiess PJ, Director EP, Rosenberg SA (1987) Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol

    Google Scholar 

  97. 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. N Engl J Med 319:1676–1680

    Article  CAS  Google Scholar 

  98. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. https://doi.org/10.1038/nature12213

  99. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM et al (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science (80-. ). https://doi.org/10.1126/science.1076514

  100. Kessels HWHG, Wolkers MC, Van Den Boom MD, Van Den Valk MA, Schumacher TNM (2001) Immunotherapy through TCR gene transfer. Nat Immunol. https://doi.org/10.1038/ni1001-957

  101. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalían SL, Kammula US, Restifo NP et al (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (80-. ). https://doi.org/10.1126/science.1129003

  102. Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan DAN, Lanier BJ et al (2010) Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. https://doi.org/10.1182/blood-2010-04-281931

  103. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. https://doi.org/10.1056/NEJMoa1003466

  104. Duong CPM, Yong CSM, Kershaw MH, Slaney CY, Darcy PK (2015) Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol Immunol. https://doi.org/10.1016/j.molimm.2014.12.009

  105. Thaxton JE, Li Z (2014) To affinity and beyond: harnessing the T cell receptor for cancer immunotherapy. Hum Vaccin Immunother. https://doi.org/10.4161/21645515.2014.973314

  106. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR et al (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood. https://doi.org/10.1182/blood-2009-03-211714

  107. Chmielewski M, Hombach A, Heuser C, Adams GP, Abken H (2014) T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity. J Immunol. https://doi.org/10.4049/jimmunol.173.12.7647

  108. Jena B, Dotti G, Cooper LJN (2010) Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. https://doi.org/10.1182/blood-2010-01-043737

  109. Gross G, Waks T, Eshhar Z (1989) Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci 86:10024–10028

    Article  CAS  Google Scholar 

  110. Maher J, Brentjens RJ, Gunset G, Rivière I, Sadelain M (2002) Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ/CD28 receptor. Nat Biotechnol. https://doi.org/10.1038/nbt0102-70

  111. Imai C, Mihara K, Andreansky M, Nicholson IC, Pui CH, Geiger TL, Campana D (2004) Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. https://doi.org/10.1038/sj.leu.2403302

  112. Song DG, Ye Q, Carpenito C, Poussin M, Wang LP, Ji C, Figini M, June CH, Coukos G, Powell DJ (2011) In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res. https://doi.org/10.1158/0008-5472.CAN-11-0422

  113. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M et al (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3008226

  114. Brentjens RJ, Rivière I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O et al (2011) Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. https://doi.org/10.1182/blood-2011-04-348540

  115. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF et al (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. https://doi.org/10.1056/NEJMoa1407222

  116. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN et al (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. https://doi.org/10.1016/S0140-6736(14)61403-3

  117. Couzin-Frankel J (2013) Cancer immunotherapy. Science (80-. ) 342:1432–1433

    Article  CAS  Google Scholar 

  118. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA (2010) Case report of a serious adverse event following the administration of t cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. https://doi.org/10.1038/mt.2010.24

  119. Klebanoff CA, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones AR, Finkelstein SE, Palmer DC, Antony PA, Hwang ST, Rosenberg SA et al (2005) Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.0503726102

  120. Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP (2006) Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. https://doi.org/10.1038/nri1842

  121. Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, Finkelstein SE, Theoret MR, Rosenberg SA, Restifo NP (2005) Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest. https://doi.org/10.1172/JCI24480

  122. Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ et al (2011) Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity. https://doi.org/10.1016/j.immuni.2011.09.019

  123. Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B, Gräf P, Verschoor A, Schiemann M, Höfer T, Busch DH (2013) Disparate individual fates compose robust CD8+ T cell immunity. Science (80-. ). https://doi.org/10.1126/science.1235454

  124. Gerlach C, Rohr JC, Perié L, Van Rooij N, Van Heijst JWJ, Velds A, Urbanus J, Naik SH, Jacobs H, Beltman JB et al (2013) Heterogeneous differentiation patterns of individual CD8+T cells. Science (80-. ). https://doi.org/10.1126/science.1235487

  125. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR et al (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-11-0116

  126. Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C et al (2011) A human memory T cell subset with stem cell-like properties. Nat Med. https://doi.org/10.1038/nm.2446

  127. Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS et al (2014) Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science (80-. ). https://doi.org/10.1126/science.1251102

  128. Mitsuyasu RT, Anton PA, Deeks SG, Scadden DT, Connick E, Downs MT, Bakker A, Roberts MR, June CH, Jalali S et al (2000) Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood

    Google Scholar 

  129. Deeks SG, Wagner B, Anton PA, Mitsuyasu RT, Scadden DT, Huang C, Macken C, Richman DD, Christopherson C, June CH et al (2002) A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Mol Ther. https://doi.org/10.1006/mthe.2002.0611

  130. Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G, Hege KM, Vogel AN, Kalos M, Riley JL, Deeks SG et al (2012) Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3003761

  131. Hütter G, Nowak D, Mossner M, Ganepola S, Müßig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O et al (2009) Long-term control of HIV by CCR5 Delta 32/Delta32 stem-cell transplantation. N Engl J Med 360:692–698

    Article  Google Scholar 

  132. Liang M, Kamata M, Chen KN, Pariente N, An DS, Chen ISY (2010) Inhibition of HIV-1 infection by a unique short hairpin RNA to chemokine receptor 5 delivered into macrophages through hematopoietic progenitor cell transduction. J Gene Med. https://doi.org/10.1002/jgm.1440

  133. Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL et al (2008) Establishment of HIV-1 resistance in CD4 + T cells by genome editing using zinc-finger nucleases. Nat Biotechnol. https://doi.org/10.1038/nbt1410

  134. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR (2002) Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. https://doi.org/10.1056/nejm199510193331603

  135. Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H et al (2010) Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. https://doi.org/10.1097/CJI.0b013e3181f3cbf4

  136. Neuenhahn M, Albrecht J, Odendahl M, Schlott F, Dössinger G, Schiemann M, Lakshmipathi S, Martin K, Bunjes D, Harsdorf S et al (2017) Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after Allo-HSCT. Leukemia. https://doi.org/10.1038/leu.2017.16

  137. O’Reilly RJ, Prockop S, Hasan AN, Koehne G, Doubrovina E (2016) Virus-specific T-cell banks for ‘off the shelf’ adoptive therapy of refractory infections. Bone Marrow Transplant. https://doi.org/10.1038/bmt.2016.17

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Md. Imtaiyaz Hassan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dahiya, R., Mohammad, T., Hassan, M.I. (2020). Genome Engineering Tools in Immunotherapy. In: Singh, S. (eds) Systems and Synthetic Immunology . Springer, Singapore. https://doi.org/10.1007/978-981-15-3350-1_3

Download citation

Publish with us

Policies and ethics