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Critical Reviews™ in Immunology

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The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) IF: 1.3 To calculate the five year Impact Factor, citations are counted in 2017 to the previous five years and divided by the source items published in the previous five years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) 5-Year IF: 2.6 The Eigenfactor score, developed by Jevin West and Carl Bergstrom at the University of Washington, is a rating of the total importance of a scientific journal. Journals are rated according to the number of incoming citations, with citations from highly ranked journals weighted to make a larger contribution to the eigenfactor than those from poorly ranked journals. Eigenfactor: 0.00079 The Journal Citation Indicator (JCI) is a single measurement of the field-normalized citation impact of journals in the Web of Science Core Collection across disciplines. The key words here are that the metric is normalized and cross-disciplinary. JCI: 0.24 SJR: 0.429 SNIP: 0.287 CiteScore™:: 2.7 H-Index: 81

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Structural Determinants of Chimeric Antigen Receptor Design

Volumen 41, Ausgabe 1, 2021, pp. 89-104
DOI: 10.1615/CritRevImmunol.2021037551
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ABSTRAKT

Chimeric antigen receptor (CAR) T cell therapy consists of the gene transfer of a cassette encoding a receptor capable of redirecting the transduced T cell toward a specific cytotoxic response against tumor cells. The therapy has been providing a new perspective on some hematologic malignancies, such as CD19+ lymphomas and acute lympho-blastic leukemia. CAR-T cell-based therapies are now approved for commercial distribution in different countries. Over the years, several modifications were necessary in the CAR structure to get it to its current results. CAR-T strategies still have plenty of room for improvement in order to improve clinical benefits and to overcome some of the limitations that still impair broader application. One main issue is the dysfunctional acquired phenotype, provoked by tumor inhibitory molecules or even exacerbated signaling by the CAR molecule itself. In this regard, Many research groups focus on discrete incremental modifications in each of the CAR molecule domains of the conventional structure looking for better response. Among these redesign strategies are the modulation of the binding affinity, use of costimulatory molecule ligands, and control of intracellular signaling. This review focuses on the newest reports covering structure changes in the CAR molecule capable of eliciting improved responses by transduced cells.

REFERENZEN
  1. Esfahani K, Roudaia L, Buhlaiga N, Del Rincon SV, Papneja N, Miller WH. A review of cancer immunotherapy: From the past, to the present, to the future. Curr Oncol. 2020 Apr;27(Suppl 2):S87-S97. PMCID: PMC7194005. .

  2. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: A clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008 Apr;8(4):299-308. PMCID: PMC2553205. .

  3. FDA.gov [homepage on the Internet]. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome; 2019 Sep 2 [cited 2020 Dec 12]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleu-cel-b-cell-all-and-tocilizumab-cytokine-release-syndrome. .

  4. FDA.gov [homepage on the Internet]. FDA approves axi-cabtagene ciloleucel for large B-cell lymphoma; 2019 Sep 2 [cited 2020 Dec 12]. Available from: https://www. fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-large-b-cell-lymphoma. .

  5. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8. PMCID: PMC298636. .

  6. Gross G, Gorochov G, Waks T, Eshhar Z. Generation of effector T cells expressing chimeric T cell receptor with antibody type-specificity. Transplant Proc. 1989 Feb;21(1 Pt 1):127-30. PMID: 2784887. .

  7. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002 Jan;20(1):70-5. PMID: 11753365. .

  8. Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, Campana D, Riley JL, Grupp SA, June CH. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009 Aug;17(8):1453-64. PMCID: PMC2805264. .

  9. Chicaybam L, Bonamino MH, Luckow Invitti A, Bortman Rozenchan P, de Luna Vieira I, Strauss BE. Overhauling CAR T cells to improve efficacy, safety and cost. Cancers. 2020 Sep;12(9):2360. .

  10. Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan D-AN, Lanier BJ, Morgan RA, Rosenberg SA. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010 Nov 18;116(20):4099-102. PMCID: PMC2993617. .

  11. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. PMID: 21832238. .

  12. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011 Aug 25;365(8):725-33. PMID: 21830940. .

  13. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-18. PMID: 23527958. .

  14. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-44. PM-CID: PMC5882485. .

  15. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-48. PMCID: PMC5996391. .

  16. Fraietta JA, Lacey SF, Orlando EJ, Pruteanu-Malinici I, Gohil M, Lundh S, Boesteanu AC, Wang Y, O'Connor RS, Hwang W-T, Pequignot E, Ambrose DE, Zhang C, Wilcox N, Bedoya F, Dorfmeier C, Chen F, Tian L, Parakandi H, Gupta M, Young RM, Johnson FB, Kulikovskaya I, Liu L, Xu J, Kassim SH, Davis MM, Levine BL, Frey NV, Siegel DL, Huang AC, Wherry EJ, Bitter H, Brogdon JL, Porter DL, June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med. 2018 May;24(5):563-71. .

  17. Cheng J, Zhao L, Zhang Y, Qin Y, Guan Y, Zhang T, Liu C, Zhou J. Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies. Front Oncol [Internet]. 2019 Nov 21 [cited 2020 Dec 28];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6882288/ PMCID: PMC6882288. .

  18. Acuto O, Michel F. CD28-mediated co-stimulation: A quantitative support for TCR signalling. Nat Rev Immunol. 2003 Dec;3(12):939-51. PMID: 14647476. .

  19. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591-619. PMCID: PMC2740335. .

  20. Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, Kaplan RN, Patterson GH, Fry TJ, Orentas RJ, Mackall CL. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nature Med. 2015 Jun;21(6):581-90. .

  21. Hudecek M, Lupo-Stanghellini M-T, Kosasih PL, Sommermeyer D, Jensen MC, Rader C, Riddell SR. Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. Clin Cancer Res. 2013 Jun 15;19(12):3153-64. PMID: 23620405. .

  22. Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A, Boesteanu AC, Cogdill AP, Chen T, Fraietta JA, Kloss CC, Posey AD, Engels B, Singh R, Ezell T, Idamakanti N, Ramones MH, Li N, Zhou L, Plesa G, Seykora JT, Okada H, June CH, Brogdon JL, Maus MV. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med. 2015 Feb 18;7(275):275ra22. .

  23. Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H, Lee DA, Heimberger AB, Champlin RE, Cooper LJN. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res. 2015 Sep 1;75(17):3505-18. .

  24. Chmielewski M, Hombach A, Heuser C, Adams GP, Abken H. T cell activation by antibody-like immunore-ceptors: 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. 2004 Dec 15;173(12):7647-53. PMID: 15585893. .

  25. Castellarin M, Sands C, Da T, Scholler J, Graham K, Buza E, Fraietta JA, Zhao Y, June CH. A rational mouse model to detect on-target, off-tumor CAR T cell toxicity. JCI Insight [Internet]. 2020 Jul 23 [cited 2020 Sep 16];5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7453898/ PMCID: PMC7453898. .

  26. Chicaybam L, Bonamino MH. Moving receptor redirected adoptive cell therapy toward fine tuning of antitumor responses. Int Rev Immunol. 2014 0ct;33(5):402-16. PMID: 24911925. .

  27. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010 Apr;18(4):843-51. PMCID: PMC2862534 .

  28. Thokala R, Olivares S, Mi T, Maiti S, Deniger D, Huls H, Torikai H, Singh H, Champlin RE, Laskowski T, Mc-Namara G, Cooper LJN. Redirecting specificity of T cells using the sleeping beauty system to express chimeric antigen receptors by mix-and-matching of VL and VH domains targeting CD123+ tumors. PLoS One. 2016 Aug 22;11(8):e0159477. .

  29. Wardemann H, Hammersen J, Nussenzweig MC. Human autoantibody silencing by immunoglobulin light chains. J Exp Med. 2004 Jul 19;200(2):191-9. .

  30. Drent E, Themeli M, Poels R, de Jong-Korlaar R, Yuan H, de Bruijn J, Martens ACM, Zweegman S, van de Donk NWCJ, Groen RWJ, Lokhorst HM, Mutis T. A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Mol Ther. 2017;25(8):1946-58. PMCID: PMC5542711. .

  31. Clarke SC, Ma B, Trinklein ND, Schellenberger U, Osborn MJ, Ouisse L-H, Boudreau A, Davison LM, Harris KE, Ugamraj HS, Balasubramani A, Dang KH, Jorgensen B, Ogana HAN, Pham DT, Pratap PP, Sankaran P, Anegon I, van Schooten WC, Bruggemann M, Buelow R, Force Aldred S. Multispecific antibody development platform based on human heavy chain antibodies. Front Immunol [Internet]. 2019 [cited 2020 Nov 2];9. Available from:https://www.frontiersin.org/articles/10.3389/fimmu. 2018.03037/full. .

  32. Lam N, Trinklein ND, Buelow B, Patterson GH, Ojha N, Kochenderfer JN. Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains. Nature Commun. 2020 Jan 15;11(1):283. .

  33. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hammers C, Songa EB, Bendahman N, Hammers R. Naturally occurring antibodies devoid of light chains. Nature. 1993 Jun;363(6428):446-8. .

  34. Iri-Sofla FJ, Rahbarizadeh F, Ahmadvand D, Rasaee MJ. Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by PhiC31 integrase. Exper Cell Res. 2011 Nov 1;317(18):2630-41. .

  35. Hajari Taheri F, Hassani M, Sharifzadeh Z, Behdani M, Arashkia A, Abolhassani M. T cell engineered with a novel nanobody-based chimeric antigen receptor against VEGFR2 as a candidate for tumor immunotherapy. IUBMB Life. 2019;71(9):1259-67. PMID: 30724452. .

  36. Xie YJ, Dougan M, Jailkhani N, Ingram J, Fang T, Kummer L, Momin N, Pishesha N, Rickelt S, Hynes RO, Ploegh H. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proc Natl Acad Sci U S A. 2019 16;116(16):7624-31. PMCID: PMC6475367. .

  37. Han X, Cinay GE, Zhao Y, Guo Y, Zhang X, Wang P. Adnectin-based design of chimeric antigen receptor for T cell engineering. Mol Ther. 2017 01;25(11):2466-76. PMCID: PMC5675441. .

  38. Spear P, Wu M-R, Sentman M-L, Sentman CL. NKG2D ligands as therapeutic targets. Cancer Immun [Internet]. 2013 May 1 [cited 2020 Nov 25];13. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3700746/. PM-CID: PMC3700746. .

  39. Zhang T, Lemoi BA, Sentman CL. Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy. Blood. 2005 May 12;106(5):1544-51. PMID: 15890688. .

  40. Lehner M, Gotz G, Proff J, Schaft N, Dorrie J, Full F, Ensser A, Muller YA, Cerwenka A, Abken H, Parolini O, Ambros PF, Kovar H, Holter W. Redirecting T cells to Ewing's sarcoma family of tumors by a chimeric NKG2D receptor expressed by lentiviral transduction or mRNA transfection. PLoS One. 2012;7(2):e31210. PMCID: PMC3280271. .

  41. Song D-G, Ye Q, Santoro S, Fang C, Best A, Powell DJ. Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition. Human Gene Ther. 2013 Jan 8;24(3):295-305. .

  42. Davies DM, Foster J, van der Stegen SJC, Parente-Pereira AC, Chiapero-Stanke L, Delinassios GJ, Burbridge SE, Kao V, Liu Z, Bosshard-Carter L, van Schalkwyk MCI, Box C, Eccles SA, Mather SJ, Wilkie S, Maher J. Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells. Mol Med. 2012 Feb 17;18(1):565-76. PMCID: PMC3388141. .

  43. Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, Arteaga CL. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007 Aug 15;13(16):4909-19. PMID: 17699871. .

  44. Kong S, Sengupta S, Tyler B, Bais AJ, Ma Q, Doucette S, Zhou J, Sahin A, Carter BS, Brem H, Junghans RP, Sampath P. Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Clin Cancer Res. 2012 Nov 1;18(21):5949-60. PMCID: PMC4337849. .

  45. Krebs S, Chow KK, Yi Z, Rodriguez-Cruz T, Hegde M, Gerken C, Ahmed N, Gottschalk S. T cells redirected to IL13Ra2 with IL13 mutein-CARs have antiglioma activity but also recognize IL13Ra1. Cytotherapy. 2014 Aug;16(8):1121-31. PMCID: PMC4087074. .

  46. Brown CE, Badie B, Barish ME, Weng L, Ostberg JR, Chang W-C, Naranjo A, Starr R, Wagner J, Wright C, Zhai Y, Bading JR, Ressler JA, Portnow J, D'Apuzzo M, Forman SJ, Jensen MC. Bioactivity and safety of IL-13Ra2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015 Sep 15;21(18):4062-72. PMCID: PMC4632968. .

  47. Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D'Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. Massachusetts Medical Society [Internet]. 2016 [cited 2020 Dec 5]. Available from: https://www.nejm. org/doi/10.1056/NEJMoa1610497. .

  48. Romeo C, Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037-46. PMID: 1900456. .

  49. Deeks SG, Wagner B, Anton PA, Mitsuyasu RT, Scadden DT, Huang C, Macken C, Richman DD, Christopherson C, June CH, Lazar R, Broad DF, Jalali S, Hege KM. A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Mol Ther. 2002 Jun 1;5(6):788-97. .

  50. Kumaresan PR, Manuri PR, Albert ND, Maiti S, Singh H, Mi T, Roszik J, Rabinovich B, Olivares S, Krishnamurthy J, Zhang L, Najjar AM, Huls MH, Lee DA, Champlin RE, Kontoyiannis DP, Cooper LJN. Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10660-5. PMID: 25002471. .

  51. Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ, Zenzo GD, Lanzavecchia A, Seykora JT, Cotsarelis G, Milone MC, Payne AS. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016 Jul 8;353(6295):179-84. PMID: 27365313. .

  52. Mazzi MT, Hajdu KL, Ribeiro PR, Bonamino MH. CAR-T cells leave the comfort zone: Current and future applications beyond cancer. Immunother Advanc [Internet]. 2020 Nov 25 [cited 2020 Dec 6];1. Available from: https:// academic.oup.com/immunotherapyadv/advance-article/ doi/10.1093/immadv/ltaa006/5999886. .

  53. Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV, Heller G, Sadelain M. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nature Med. 2007 Dec;13(12):1440-9. .

  54. Zhao Z, Condomines M, van der Stegen SJC, Perna F, Kloss CC, Gunset G, Plotkin J, Sadelain M. Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell. 2015 Oct 12;28(4):415-28. PMCID: PMC5003056. .

  55. Nguyen P, Okeke E, Clay M, Haydar D, Justice J, O'Reilly C, Pruett-Miller S, Papizan J, Moore J, Zhou S, Throm R, Krenciute G, Gottschalk S, DeRenzo C. Route of 41BB/41BBL costimulation determines effector function of B7-H3-CAR.CD28Z T cells. Mol Ther Oncolyt. 2020 Sep 25;18:202-14. .

  56. Park JH, Palomba ML, Batlevi CL, Riviere I, Wang X, Senechal B, Furman RR, Bernal Y, Hall M, Pineda J, Diamonte C, Halton E, Brentjens RJ, Sadelain M. A phase I first-in-human clinical trial of CD19-targeted 19-28z/4-1BBL armored CAR T cells in patients with relapsed or refractory NHL and CLL including Richter's transformation. Blood. 2018 Nov 29;132(Suppl 1):224. .

  57. Curran KJ, Seinstra BA, Nikhamin Y, Yeh R, Usachenko Y, van Leeuwen DG, Purdon T, Pegram HJ, Brentjens RJ. Enhancing antitumor efficacy of chimeric antigen receptor T cells through constitutive CD40L expression. Mol Ther. 2015 Apr;23(4):769-78. PMCID: PMC4395796. .

  58. Liao Q, Mao Y, He H, Ding X, Zhang X, Xu J. PD-L1 chimeric costimulatory receptor improves the efficacy of CAR-T cells for PD-L1-positive solid tumors and reduces toxicity in vivo. Biomarker Res. 2020 Nov 2;8(1):57. .

  59. Hurton LV, Singh H, Najjar AM, Switzer KC, Mi T, Maiti S, Olivares S, Rabinovich B, Huls H, Forget M-A, Datar V, Kebriaei P, Lee DA, Champlin RE, Cooper LJN. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7788-97. .

  60. Alizadeh D, Wong RA, Yang X, Wang D, Pecoraro JR, Kuo C-F, Aguilar B, Qi Y, Ann DK, Starr R, Urak R, Wang X, Forman SJ, Brown CE. IL15 enhances CAR-T cell antitumor activity by reducing mTORC1 activity and preserving their stem cell memory phenotype. Cancer Immunol Res. 2019 May 1;7(5):759-72. PMID: 30890531. .

  61. Arcangeli S, Falcone L, Camisa B, De Girardi F, Biondi M, Giglio F, Ciceri F, Bonini C, Bondanza A, Casucci M. Next-generation manufacturing protocols enriching TSCM CAR T cells can overcome disease-specific T cell defects in cancer patients. Front Immunol [Internet]. 2020 Jun 19 [cited 2020 Dec 7];11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317024/ PM-CID: PMC7317024. .

  62. Shimabukuro-Vornhagen A, Godel P, Subklewe M, Stemmler HJ, SchloBer HA, Schlaak M, Kochanek M, Boll B, von Bergwelt-Baildon MS. Cytokine release syndrome. J ImmunoTher Cancer. 2018 Jun 15;6(1):56. .

  63. Tan AHJ, Vinanica N, Campana D. Chimeric antigen receptor T cells with cytokine neutralizing capacity. Blood Adv. 2020 Apr 14;4(7):1419-31. .

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

  65. Hudecek M, Sommermeyer D, Kosasih PL, Silva-Benedict A, Liu L, Rader C, Jensen MC, Riddell SR. The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol Res. 2015 Feb;3(2):125-35. PMCID: PMC4692801. .

  66. Alabanza L, Pegues M, Geldres C, Shi V, Wiltzius JJW, Sievers SA, Yang S, Kochenderfer JN. Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains. Mol Ther. 2017 01;25(11):2452-65. PMCID: PMC5675490. .

  67. Majzner RG, Rietberg SP, Sotillo E, Dong R, Vachharajani VT, Labanieh L, Myklebust JH, Kadapakkam M, Weber EW, Tousley AM, Richards RM, Heitzeneder S, Nguyen SM, Wiebking V, Theruvath J, Lynn RC, Xu P, Dunn AR, Vale RD, Mackall CL. Tuning the antigen density requirement for CAR T-cell activity. Cancer Discov. 2020 May;10(5):702-23. PMID: 32193224. .

  68. Till BG, Jensen MC, Wang J, Qian X, Gopal AK, Maloney DG, Lindgren CG, Lin Y, Pagel JM, Budde LE, Raubitschek A, Forman SJ, Greenberg PD, Riddell SR, Press OW. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: Pilot clinical trial results. Blood. 2012 Apr 26;119(17):3940-50. PMCID: PMC3350361. .

  69. Bridgeman JS, Hawkins RE, Bagley S, Blaylock M, Holland M, Gilham DE. The optimal antigen response of chimeric antigen receptors harboring the CD3Z transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol. 2010 Jun 15;184(12):6938-49. PMID: 20483753. .

  70. Guest RD, Hawkins RE, Kirillova N, Cheadle EJ, Arnold J, O'Neill A, Irlam J, Chester KA, Kemshead JT, Shaw DM, Embleton MJ, Stern PL, Gilham DE. The role of ex-tracellular spacer regions in the optimal design of chimeric immune receptors: Evaluation of four different scFvs and antigens. J Immunother. 2005 Jun;28(3):203-11. PMID: 15838376. .

  71. Wilkie S, Picco G, Foster J, Davies DM, Julien S, Cooper L, Arif S, Mather SJ, Taylor-Papadimitriou J, Burchell JM, Maher J. Retargeting of human T cells to tumor-associated MUC1: The evolution of a chimeric antigen receptor. J Immunol. 2008 Apr 1;180(7):4901-09. PMID: 18354214. .

  72. Fujiwara K, Tsunei A, Kusabuka H, Ogaki E, Tachibana M, Okada N. Hinge and transmembrane domains of chimeric antigen receptor regulate receptor expression and signaling threshold. Cells. 2020;9(5):1182. PMCID: PMC7291079. .

  73. Leddon SA, Fettis MM, Abramo K, Kelly R, Oleksyn D, Miller J. The CD28 transmembrane domain contains an essential dimerization motif. Front Immunol [Internet]. 2020 [cited 2020 Nov 8];11. Available from: https:// www.frontiersin.org/articles/10.3389/fimmu.2020.01519/ full#B52. .

  74. Kinnear G, Jones ND, Wood KJ. Costimulation blockade: Current perspectives and implications for therapy. Transplantation. 2013 Feb 27;95(4):527-35. PMCID: PMC3580065. .

  75. Teijeira A, Garasa S, Etxeberria I, Gato-Canas M, Melero I, Delgoffe GM. Metabolic consequences of T-cell co-stimulation in anticancer immunity. Cancer Immunol Res. 2019 Oct 1;7(10):1564-9. PMID: 31575551. .

  76. Weinkove R, George P, Dasyam N, McLellan AD. Selecting costimulatory domains for chimeric antigen receptors: Functional and clinical considerations. Clin Transl Immunol. 2019;8(5):e1049. PMCID: PMC6511336. .

  77. Finney HM, Akbar AN, Lawson ADG. Activation of resting human primary T cells with chimeric receptors: Co-stimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol. 2004 Jan 1;172(1):104-13. PMID: 14688315. .

  78. Hombach AA, Chmielewski M, Rappl G, Abken H. Adoptive immunotherapy with redirected T cells produces CCR7-cells that are trapped in the periphery and benefit from combined CD28-0X40 costimulation. Hum Gene Ther. 2013 Mar;24(3):259-69. PMID: 23350854. .

  79. Hombach AA, Heiders J, Foppe M, Chmielewski M, Abken H. OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4(+) T cells. Oncoimmunology. 2012 Jul 1;1(4):458-66. PMCID: PMC3382912. .

  80. Kintz H, Nylen E, Barber A. Inclusion of Dap10 or 4-1BB costimulation domains in the chPD1 receptor enhances anti-tumor efficacy of T cells in murine models of lymphoma and melanoma. Cell Immunol. 2020 May;351:104069. PMID: 32106933. .

  81. Abken H. Costimulation engages the gear in driving CARs. Immunity. 2016 Feb16;44(2):214-6. PMID: 26885852. .

  82. Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, Varela-Rohena A, Haines KM, Heitjan DF, Albelda SM, Carroll RG, Riley JL, Pastan I, June CH. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3360-5. PMCID: PMC2651342. .

  83. Sun C, Shou P, Du H, Hirabayashi K, Chen Y, Herring LE, Ahn S, Xu Y, Suzuki K, Li G, Tsahouridis O, Su L, Savoldo B, Dotti G. THEMIS-SHP1 recruitment by 4-1BB tunes LCK-mediated priming of chimeric antigen receptor-re-directed T cells. Cancer Cell. 2020 10;37(2):216-25.e6. PMCID: PMC7397569. .

  84. Boucher JC, Li G, Kotani H, Cabral ML, Morrissey D, Lee SB, Spitler K, Beatty NJ, Cervantes EV, Shrestha B, Yu B, Kazi A, Wang X, Sebti SM, Davila ML. CD28 costimulatory domain-targeted mutations enhance chimeric antigen receptor T-cell function. Cancer Immunol Res [Internet]. 2020 Nov 13 [cited 2020 Dec 12]. Available from: https://cancerimmunolres.aacrjournals.org/ content/early/2020/12/09/2326-6066.CIR-20-0253 PMID: 33188139. .

  85. Guedan S, Madar A, Casado-Medrano V, Shaw C, Wing A, Liu F, Young RM, June CH, Posey AD. Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability. J Clin Invest. 2020 Jun 1;130(6):3087-97. PMCID: PMC7260017. .

  86. Narayanan P, Lapteva N, Seethammagari M, Levitt JM, Slawin KM, Spencer DM. A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy. J Clin Invest. 2011 Apr;121(4):1524-34. PMCID: PMC3069772. .

  87. Deguine J, Barton GM. MyD88: A central player in innate immune signaling. F1000Prime Rep. 2014;6:97. PMCID: PMC4229726. .

  88. Mata M, Gerken C, Nguyen P, Krenciute G, Spencer DM, Gottschalk S. Inducible activation of MyD88 and CD40 in CAR T cells results in controllable and potent antitumor activity in preclinical solid tumor models. Cancer Discov. 2017;7(11):1306-19. PMCID: PMC5780189. .

  89. Foster AE, Mahendravada A, Shinners NP, Chang W-C, Crisostomo J, Lu A, Khalil M, Morschl E, Shaw JL, Saha S, Duong MT, Collinson-Pautz MR, Torres DL, Rodriguez T, Pentcheva-Hoang T, Bayle JH, Slawin KM, Spencer DM. Regulated expansion and survival of chimeric antigen receptor-modified T cells using small molecule-dependent inducible MyD88/CD40. Mol Ther. 2017 06;25(9):2176-88. PMCID: PMC5589084. .

  90. Ma Y, Lim YJ, Benda A, Goyette J, Gaus K. Clustering of CD3Z is sufficient to initiate T cell receptor signaling. bioRxiv [Internet]. 2020 Feb 19 [cited 2020 Nov 16]. Available from: https://www.biorxiv.org/content/10.1101 /2020.02.17.953463v1. .

  91. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720-724. PMCID: PMC45737. .

  92. Haynes NM, Snook MB, Trapani JA, Cerruti L, Jane SM, Smyth MJ, Darcy PK. Redirecting mouse CTL against colon carcinoma: Superior signaling efficacy of single-chain variable domain chimeras containing TCR-Z vs. FcsRI-y. J Immunol. 2001 Jan 1;166(1):182-7. PMID: 11123291. .

  93. Irving BA, Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891-901. PMID: 1705867. .

  94. Shores EW, Ono M, Kawabe T, Sommers CL, Tran T, Lui K, Udey MC, Ravetch J, Love PE. T cell development in mice lacking all T cell receptor Z family members (Z, n, and FcsRIy). J Exp Med. 1998 Apr 6;187(7):1093-101. .

  95. Zhao Y, Wang QJ, Yang S, Kochenderfer JN, Zheng Z, Zhong X, Sadelain M, Eshhar Z, Rosenberg SA, Morgan RA. A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity. J Immunol. 2009 Nov 1;183(9):5563-74. PMID: 19843940. .

  96. Feucht J, Sun J, Eyquem J, Ho Y-J, Zhao Z, Leibold J, Dobrin A, Cabriolu A, Hamieh M, Sadelain M. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nat Med. 2019 Jan;25(1):82-88. .

  97. Wu W, Zhou Q, Masubuchi T, Shi X, Li H, Xu X, Huang M, Meng L, He X, Zhu H, Gao S, Zhang N, Jing R, Sun J, Wang H, Hui E, Wong CC, Xu C. Multiple signaling roles of CD3s and its application in CAR-T cell therapy. Cell. 2020 Aug 20;182(4):855-71.e23. PMID: 32730808. .

  98. Love PE, Hayes SM. ITAM-mediated signaling by the T-cell antigen receptor. Cold Spring Harb Perspect Biol. 2010 Jan 6;2(6):a002485. .

  99. Li L, Guo X, Shi X, Li C, Wu W, Yan C, Wang H, Li H, Xu C. Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling. Proc Natl Acad Sci U S A. 2017 18;114(29):E5891-9. PMCID: PMC5530670. .

  100. Ben Mkaddem S, Benhamou M, Monteiro RC. Under-standing Fc receptor involvement in inflammatory diseases: From mechanisms to new therapeutic tools. Front Immunol. 2019;10:811. PMCID: PMC6481281. .

  101. Hartl FA, Beck-Garcia E, Woessner NM, Flachsmann LJ, Cardenas RM-HV, Brandl SM, Taromi S, Fiala GJ, Morath A, Mishra P, Yousefi OS, Zimmermann J, Hoefflin N, Kohn M, Wohrl BM, Zeiser R, Schweimer K, Gunther S, Schamel WW, Minguet S. Noncanonical binding of Lck to CD3s promotes TCR signaling and CAR function. Nat Immunol. 2020;21(8):902-13. PMID: 32690949. .

  102. Gomes-Silva D, Mukherjee M, Srinivasan M, Krenciute G, Dakhova O, Zheng Y, Cabral JMS, Rooney CM, Orange JS, Brenner MK, Mamonkin M. Tonic 4-1BB co-stimulation in chimeric antigen receptors impedes T cell survival and is vector-dependent. Cell Rep. 2017 Oct 3;21(1):17-26. PMCID: PMC5645034. .

  103. Chen X, Khericha M, Lakhani A, Meng X, Salvestrini E, Chen LC, Shafer A, Alag A, Ding Y, Nicolaou D, Park JO, Chen YY. Rational tuning of CAR tonic signaling yields superior T-cell therapy for cancer. bioRxiv. 2020 Oct 2. doi: 10.1101/2020.10.01.322990. .

  104. Li W, Qiu S, Chen J, Jiang S, Chen W, Jiang J, Wang F, Si W, Shu Y, Wei P, Fan G, Tian R, Wu H, Xu C, Wang H. Chimeric antigen receptor designed to prevent ubiquitination and downregulation showed durable antitumor efficacy. Immunity. 2020 Aug 18;53(2):456-70. e6. .

  105. 105. Naramura M, Jang I-K, Kole H, Huang F, Haines D, Gu H. c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Nature Immunol. 2002 Dec;3(12):1192-9. .

  106. 106. Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJC, Hamieh M, Cunanan KM, Odak A, Gonen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017 Mar;543(7643):113-7. .

  107. 107. Davenport AJ, Jenkins MR, Cross RS, Yong CS, Prince HM, Ritchie DS, Trapani JA, Kershaw MH, Darcy PK, Neeson PJ. CAR-T cells inflict sequential killing of multiple tumor target cells. Cancer Immunol Res. 2015 May;3(5):483-94. PMID: 25711536. .

  108. 108. Barber A, Sentman CL. NKG2D receptor regulates human effector T-cell cytokine production. Blood. 2011 Jun 16;117(24):6571-81. PMCID: PMC3123023. .

  109. 109. Sentman CL, Meehan KR. NKG2D CARs as cell therapy for cancer. Cancer J. 2014;20(2):156-9. PMCID: PMC4017323. .

  110. 110. Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999 Jul 30;285(5428):730-2. PMID: 10426994. .

  111. 111. Ng Y-Y, Tay JCK, Li Z, Wang J, Zhu J, Wang S. T Cells expressing NKG2D CAR with a DAP12 signaling domain stimulate lower cytokine production while effective in tumor eradication. Mol Ther [Internet]. 2020 Sep 5 [cited 2020 Nov 28]. Available from: https://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/ S1525-0016(20)30426-3 PMID: 32956627. .

  112. 112. Levine BL, Miskin J, Wonnacott K, Keir C. Global manufacturing of CAR T cell therapy. Mol Ther Methods Clin Dev. 2017 Mar 17;4:92-101. PMCID: PMC5363291. .

  113. 113. Wang W, Jiang J, Wu C. CAR-NK for tumor immunotherapy: Clinical transformation and future prospects. Cancer Lett. 2020 Mar 1;472:175-80. PMID: 31790761. .

  114. 114. Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE, Cummins KD, Shen F, Shan X, Veliz K, Blouch K, Yashiro-Ohtani Y, Kenderian SS, Kim MY, O'Connor RS, Wallace SR, Kozlowski MS, Marchione DM, Shestov M, Garcia BA, June CH, Gill S. Human chimeric antigen receptor macrophages for c ancer immunotherapy. Nat B iotechno l. 2020Aug;38(8): 947-53. .

  115. 115. Ghassemi S, Nunez-Cruz S, O'Connor RS, Fraietta JA, Patel PR, Scholler J, Barrett DM, Lundh SM, Davis MM, Bedoya F, Zhang C, Leferovich J, Lacey SF, Levine BL, Grupp SA, June CH, Melenhorst JJ, Milone MC. Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells. Cancer Immunol Res. 2018 Sep 1;6(9):1100-9. PMID: 30030295. .

  116. 116. Abdo LM, Barros LRC, Viegas MS, Marques LVC, Ferreira P de S, Chicaybam L, Bonamino MH. Development of CAR-T cell therapy for B-ALL using a point-of-care approach. OncoImmunology. 2020 Jan 1;9(1): 1752592. .

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