CoChat
Sign Up
Cited by 14CAR-T cell therapy researchImmunotherapy and Immune ResponsesVirus-based gene therapy research

Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors

Open access
Lo Presti, Vania, Buitenwerf, Frank, van Til, Niek P., Nierkens, Stefan·2020·Vaccines
DOI 10.3390/vaccines8040733PMC PMC7761868
Open this paper in CoChat — free accountOpen PDF

Abstract

Recent developments in gene engineering technologies have drastically improved the therapeutic treatment options for cancer patients. The use of effective chimeric antigen receptor T (CAR-T) cells and recombinant T cell receptor engineered T (rTCR-T) cells has entered the clinic for treatment of hematological malignancies with promising results. However, further fine-tuning, to improve functionality and safety, is necessary to apply these strategies for the treatment of solid tumors. The immunosuppressive microenvironment, the surrounding stroma, and the tumor heterogeneity often results in poor T cell reactivity, functionality, and a diminished infiltration rates, hampering the efficacy of the treatment. The focus of this review is on recent advances in rTCR-T cell therapy, to improve both functionality and safety, for potential treatment of solid tumors and provides an overview of ongoing clinical trials. Besides selection of the appropriate tumor associated antigen, efficient delivery of an optimized recombinant TCR transgene into the T cells, in combination with gene editing techniques eliminating the endogenous TCR expression and disrupting specific inhibitory pathways could improve adoptively transferred T cells. Armoring the rTCR-T cells with specific cytokines and/or chemokines and their receptors, or targeting the tumor stroma, can increase the infiltration rate of the immune cells within the solid tumors. On the other hand, clinical “off-tumor/on-target” toxicities are still a major potential risk and can lead to severe adverse events. Incorporation of safety switches in rTCR-T cells can guarantee additional safety. Recent clinical trials provide encouraging data and emphasize the relevance of gene therapy and gene editing tools for potential treatment of solid tumors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/vaccines8040733

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TCR-T cell therapy has shown relative effectiveness in the treatment of solid tumors compared to CAR-T cell therapy due to the ability of TCR-T cells to recognize both intracellular and extracellular proteins.

    “TCR-T cell therapy has shown relative effectiveness in the treatment of solid tumors compared to CAR-T cell therapy due to the ability of TCR-T cells to recognize both intracellular and extracellular proteins.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [277]

    Section 1 says rTCR-T cells can recognize peptides from both extracellular and intracellular proteins, a major advantage over CAR-T cells, and that CAR-T treatment has been less effective for solid tumors. It describes the resulting advantage for rTCR-T treatment as potential, however; it does not establish that TCR-T therapy has shown superior clinical effectiveness against solid tumors. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 112 · Cited by 14

Research works printed but not linked: 104

  1. [1]Yang Y. Cancer immunotherapy: Harnessing the immune system to battle cancer Find the latest version: Cancer immunotherapy: Harnessing the immune system to battle cancer J. Clin. Investig. 2015 125 3335 3337 10.1172/JCI83871 26325031 PMC4588312 · DOI
  2. [2]Hargadon K.M. Johnson C.E. Williams C.J. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors Int. Immunopharmacol. 2018 62 29 39 10.1016/j.intimp.2018.06.001 29990692 · DOI · Paper page
  3. [3]Pitt J.M. Vétizou M. Daillère R. Roberti M.P. Yamazaki T. Routy B. Lepage P. Boneca I.G. Chamaillard M. Kroemer G. Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors Immunity 2016 44 1255 1269 10.1016/j.immuni.2016.06.001 27332730 · DOI
  4. [4]Dudley M.E. Rosenberg S.A. Adoptive-cell-transfer therapy for the treatment of patients with cancer Nat. Rev. Cancer 2003 3 666 675 10.1038/nrc1167 12951585 PMC2305722 · DOI
  5. [5]Dudley M.E. Wunderlich J.R. Robbins P.F. Yang J.C. Hwu P. Schwartzentruber D.J. Topalian S.L. Sherry R. Restifo N.P. Hubicki A.M. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes Science 2002 298 850 854 10.1126/science.1076514 12242449 PMC1764179 · DOI · Paper page
  6. [6]Li D. Li X. Zhou W.L. Huang Y. Liang X. Jiang L. Yang X. Sun J. Li Z. Han W.D. Genetically engineered t cells for cancer immunotherapy Signal. Transduct. Target. Ther. 2019 4 10.1038/s41392-019-0070-9 PMC6799837 31637014 · DOI
  7. [7]Martinez M. Moon E.K. CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment Front. Immunol. 2019 10 1 21 10.3389/fimmu.2019.00128 30804938 PMC6370640 · DOI
  8. [8]Bagley S.J. O’Rourke D.M. Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions Pharmacol. Ther. 2020 205 10.1016/j.pharmthera.2019.107419 31629009 · DOI
  9. [9]Binnewies M. Roberts E.W. Kersten K. Chan V. Fearon D.F. Merad M. Coussens L.M. Gabrilovich D.I. Ostrand-rosenberg S. Hedrick C.C. Understanding the tumor iimune microenvironment (TIME) for effective therapy Nat. Med. 2018 24 541 550 10.1038/s41591-018-0014-x 29686425 PMC5998822 · DOI · Paper page
  10. [10]Chen N. Li X. Chintala N.K. Tano Z.E. Adusumilli P.S. Driving CARs on the uneven road of antigen heterogeneity in solid tumors Curr. Opin. Immunol. 2018 51 103 110 10.1016/j.coi.2018.03.002 29554494 PMC5943172 · DOI
  11. [11]Garber K. Driving T-cell immunotherapy to solid tumors Nat. Biotechnol. 2018 36 215 219 10.1038/nbt.4090 29509745 · DOI
  12. [12]Ping Y. Liu C. Zhang Y. T-cell receptor-engineered T cells for cancer treatment: Current status and future directions Protein Cell 2018 9 254 266 10.1007/s13238-016-0367-1 28108950 PMC5829268 · DOI
  13. [13]Debets R. Donnadieu E. Chouaib S. Coukos G. TCR-engineered T cells to treat tumors: Seeing but not touching? Semin. Immunol. 2016 28 10 21 10.1016/j.smim.2016.03.002 26997556 · DOI
  14. [14]Fesnak A.D. June C.H. Levine B.L. Engineered T cells: The promise and challenges of cancer immunotherapy Nat. Rev. Cancer 2016 16 566 581 10.1038/nrc.2016.97 27550819 PMC5543811 · DOI · Paper page
  15. [15]He Q. Jiang X. Zhou X. Weng J. Targeting cancers through TCR-peptide/MHC interactions J. Hematol. Oncol. 2019 12 1 17 10.1186/s13045-019-0812-8 31852498 PMC6921533 · DOI
  16. [16]Parkhurst M.R. Yang J.C. Langan R.C. Dudley M.E. Nathan D.-A.N. Feldman S.A. Davis J.L. Morgan R.A. Merino M.J. Sherry R.M. T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis Mol. Ther. 2011 19 620 626 10.1038/mt.2010.272 21157437 PMC3048186 · DOI
  17. [17]Morgan R.A. Chinnasamy N. Abate-daga D.D. Gros A. Robbins F. Zheng Z. Feldman S.A. Yang J.C. Sherry R.M. Phan Q. Cancer regression and neurologic toxicity following anti-MAGE- A3 TCR gene therapy Richard J. Immunother. 2014 36 133 151 10.1097/CJI.0b013e3182829903 PMC3581823 23377668 · DOI
  18. [18]Linette G.P. Stadtmauer E.A. Maus M.V. Rapoport A.P. Levine B.L. Emery L. Litzky L. Bagg A. Carreno B.M. Cimino P.J. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma Blood 2013 122 863 871 10.1182/blood-2013-03-490565 23770775 PMC3743463 · DOI
  19. [19]Klebanoff C.A. Khong H.T. Antony P.A. Palmer D.C. Restifo N.P. Sinks, suppressors and antigen presenters: How lymphodepletion enhances T cell-mediated tumor immunotherapy Trends Immunol. 2005 26 111 117 10.1016/j.it.2004.12.003 15668127 PMC1388277 · DOI
  20. [20]Seliger B. Combinatorial Approaches with Checkpoint Inhibitors to Enhance Anti-tumor Immunity Front. Immunol. 2019 10 1 10 10.3389/fimmu.2019.00999 31178856 PMC6538766 · DOI
  21. [21]Inderberg-Suso E.M. Trachsel S. Lislerud K. Rasmussen A.M. Gaudernack G. Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001 Oncoimmunology 2012 1 670 686 10.4161/onci.20426 22934259 PMC3429571 · DOI
  22. [22]Cohen C.J. Gartner J.J. Horovitz-Fried M. Shamalov K. Trebska-McGowan K. Bliskovsky V.V. Parkhurst M.R. Ankri C. Prickett T.D. Crystal J.S. Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes J. Clin. Investig. 2015 125 3981 3991 10.1172/JCI82416 26389673 PMC4607110 · DOI
  23. [23]Linnemann C. Heemskerk B. Kvistborg P. Kluin R.J.C. Bolotin D.A. Chen X. Bresser K. Nieuwland M. Schotte R. Michels S. Technical Reports High-throughput identification of antigen-specific TCRs by TCR gene capture Nat. Med. 2013 19 1534 1541 10.1038/nm.3359 24121928 · DOI
  24. [24]Cole D.K. Sami M. Scott D.R. Rizkallah P.J. Borbulevych O.Y. Todorov P.T. Moysey R.K. Jakobsen B.K. Boulter J.M. Baker B.M. Increased peptide contacts govern high affinity binding of a modified TCR whilst maintaining a native pMHC docking mode Front. Immunol. 2013 4 1 8 10.3389/fimmu.2013.00168 23805144 PMC3693486 · DOI
  25. [25]Malecek K. Grigoryan A. Zhong S. Gu W.J. Johnson L.A. Rosenberg S.A. Cardozo T. Krogsgaard M. Specific Increase in Potency via Structure-Based Design of a TCR J. Immunol. 2014 193 2587 2599 10.4049/jimmunol.1302344 25070852 PMC4205480 · DOI
  26. [26]Spear T.T. Wang Y. Foley K.C. Murray D.C. Scurti G.M. Simms P.E. Garrett-Mayer E. Hellman L.M. Baker B.M. Nishimura M.I. Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells Cancer Immunol. Immunother. 2017 66 1411 1424 10.1007/s00262-017-2032-9 28634816 PMC5647210 · DOI
  27. [27]Costa C. Hypolite G. Bernadin O. Lévy C. Cosset F.-L. Asnafi V. Macintyre E. Verhoeyen E. Tesio M. Baboon envelope pseudotyped lentiviral vectors: A highly efficient new tool to genetically manipulate T-cell acute lymphoblastic leukaemia-initiating cells Leukemia 2017 31 977 980 10.1038/leu.2016.372 27922597 · DOI
  28. [28]Cavalieri S. Cazzaniga S. Geuna M. Magnani Z. Bordignon C. Naldini L. Bonini C. Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence Blood 2003 102 497 505 10.1182/blood-2003-01-0297 12649146 · DOI
  29. [29]Circosta P. Granziero L. Follenzi A. Vigna E. Stella S. Vallario A. Elia A.R. Gammaitoni L. Vitaggio K. Orso F. T Cell Receptor (TCR) Gene Transfer with Lentiviral Vectors Allows Efficient Redirection of Tumor Specificity in Naive and Memory T Cells Without Prior Stimulation of Endogenous TCR Hum. Gene Ther. 2009 20 1576 1588 10.1089/hum.2009.117 19678763 · DOI
  30. [30]Kuball J. Dossett M.L. Wolfl M. Ho W.Y. Voss R.H. Fowler C. Greenberg P.D. Facilitating matched pairing and expression of TCR chains introduced into human T cells Blood 2007 109 2331 2338 10.1182/blood-2006-05-023069 17082316 PMC1852191 · DOI
  31. [31]Sebestyén Z. Schooten E. Sals T. Zaldivar I. José E.S. Alarcón B. Bobisse S. Szöllosi J. Gratama J.W. Ralph A. Human TCR That Incorporate CD3 ζ Induce Highly Preferred Pairing between TCR α and β Chains following Gene Transfer J. Immunol. 2020 10.4049/jimmunol.180.11.7736 18490778 · DOI
  32. [32]Thomas S. Mohammed F. Reijmers R.M. Woolston A. Stauss T. Kennedy A. Stirling D. Holler A. Green L. Jones D. Framework engineering to produce dominant T cell receptors with enhanced antigen-specific function Nat. Commun. 2019 10 1 15 10.1038/s41467-019-12441-w 31575864 PMC6773850 · DOI
  33. [33]Palmer D.C. Guittard G.C. Franco Z. Crompton J.G. Eil R.L. Patel S.J. Ji Y. Van Panhuys N. Klebanoff C.A. Sukumar M. Cish actively silences TCR signaling in CD8 + T cells to maintain tumor tolerance J. Exp. Med. 2013 2095 2113 10.1084/jem.20150304 PMC4647263 26527801 · DOI
  34. [34]Duinkerken C.W. Rohaan M.W. De Weger V.A. Lohuis P.J.F.M. Latenstein M.N. Theunissen E.A.R. Balm A.J.M. Dreschler W.A. Haanen J.B.A.G. Zuur C.L. Sensorineural Hearing Loss after Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells: A Case Report and Its Pathophysiology Otol. Neurotol. 2019 40 e674 e678 10.1097/MAO.0000000000002332 31295198 · DOI
  35. [35]Morgan R.A. Dudley M.E. Wunderlich J.R. Hughes M.S. Yang J.C. Sherry R.M. Royal R.E. Topalian S.L. Kammula U.S. Restifo N.P. Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes Science 2006 314 126 129 10.1126/science.1129003 16946036 PMC2267026 · DOI · Paper page
  36. [36]Bijen H.M. van der Steen D.M. Hagedoorn R.S. Wouters A.K. Wooldridge L. Falkenburg J.H.F. Heemskerk M.H.M. Preclinical Strategies to Identify Off-Target Toxicity of High-Affinity TCRs Mol. Ther. 2018 26 1206 1214 10.1016/j.ymthe.2018.02.017 29567312 PMC5993934 · DOI
  37. [37]Bentzen A.K. Hadrup S.R. Evolution of MHC-based technologies used for detection of antigen-responsive T cells Cancer Immunol. Immunother. 2017 66 657 666 10.1007/s00262-017-1971-5 28314956 PMC5406421 · DOI
  38. [38]Shao H. Zhang W. Hu Q. Wu F. Shen H. Huang S. TCR mispairing in genetically modified T cells was detected by fluorescence resonance energy transfer Mol. Biol. Rep. 2010 37 3951 3956 10.1007/s11033-010-0053-y 20373027 · DOI
  39. [39]Bendle G.M. Linnemann C. Hooijkaas A.I. Bies L. de Witte M.A. Jorritsma A. Kaiser A.D.M. Pouw N. Debets R. Kieback E. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy Nat. Med. 2010 16 565 570 10.1038/nm.2128 20400962 · DOI
  40. [40]Legut M. Dolton G. Mian A.A. Ottmann O.G. Sewell A.K. CRISPR-mediated TCR replacement generates superior anticancer transgenic t cells Blood 2018 131 311 322 10.1182/blood-2017-05-787598 29122757 PMC5774207 · DOI
  41. [41]Provasi E. Genovese P. Lombardo A. Magnani Z. Liu P.-Q. Reik A. Chu V. Paschon D.E. Zhang L. Kuball J. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer Nat. Med. 2012 18 807 815 10.1038/nm.2700 22466705 PMC5019824 · DOI · Paper page
  42. [42]Zhang X. Cheng C. Sun W. Wang H. Engineering T Cells Using CRISPR/Cas9 for Cancer Therapy RNA Interference and CRISPR Technologies Springer Berlin, Germany 2020 Volume 2115 503 509 32006414
  43. [43]Ren J. Zhang X. Liu X. Fang C. Jiang S. A versatile system for rapid multiplex genome-edited CAR T cell generation Oncotarget 2017 8 17002 17011 10.18632/oncotarget.15218 28199983 PMC5370017 · DOI
  44. [44]Morton L.T. Reijmers R.M. Wouters A.K. Kweekel C. Remst D.F.G. Pothast C.R. Falkenburg J.H.F. Heemskerk M.H.M. Simultaneous Deletion of Endogenous TCRαβ for TCR Gene Therapy Creates an Improved and Safe Cellular Therapeutic Mol. Ther. 2020 28 64 74 10.1016/j.ymthe.2019.10.001 31636040 PMC6953894 · DOI
  45. [45]Qasim W. Zhan H. Samarasinghe S. Adams S. Amrolia P. Stafford S. Butler K. Rivat C. Wright G. Somana K. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells Sci. Transl. Med. 2017 9 eaaj2013 10.1126/scitranslmed.aaj2013 28123068 · DOI · Paper page
  46. [46]Liu X. Zhang Y. Cheng C. Cheng A.W. Zhang X. Li N. Xia C. Wei X. Liu X. Wang H. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells Cell Res. 2017 27 154 157 10.1038/cr.2016.142 27910851 PMC5223227 · DOI
  47. [47]Stadtmauer E.A. Fraietta J.A. Davis M.M. Cohen A.D. Weber K.L. Lancaster E. Mangan P.A. Kulikovskaya I. Gupta M. Chen F. CRISPR-engineered T cells in patients with refractory cancer Science 2020 367 1 64 10.1126/science.aba7365 PMC11249135 32029687 · DOI · Paper page
  48. [48]Wang J. DeClercq J.J. Hayward S.B. Li P.W.L. Shivak D.A. Gregory P.D. Lee G. Holmes M.C. Highly efficient homology-driven genome editing in human T cells by combining zinc-finger nuclease mRNA and AAV6 donor delivery Nucleic Acids Res. 2016 44 1 9 10.1093/nar/gkv1121 26527725 PMC4756813 · DOI · Paper page
  49. [49]Ortinski P.I. O’Donovan B. Dong X. Kantor B. Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR/Cas9-Mediated Gene Editing Mol. Ther. Methods Clin. Dev. 2017 5 10.1016/j.omtm.2017.04.002 PMC5424571 28497073 · DOI · Paper page
  50. [50]Hale M. Lee B. Honaker Y. Leung W.H. Grier A.E. Jacobs H.M. Sommer K. Sahni J. Jackson S.W. Scharenberg A.M. Homology-Directed Recombination for Enhanced Engineering of Chimeric Antigen Receptor T Cells Mol. Ther. Methods Clin. Dev. 2017 10.1016/j.omtm.2016.12.008 PMC5363294 28345004 · DOI
  51. [51]Eyquem J. Mansilla-soto J. Giavridis T. Van Der Stegen S.J.C. Hamieh M. Cunanan K.M. Odak A. Gönen M. Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection Nat. Publ. Gr. 2017 543 113 117 10.1038/nature21405 PMC5558614 28225754 · DOI · Paper page
  52. [52]MacLeod D.T. Antony J. Martin A.J. Moser R.J. Hekele A. Wetzel K.J. Brown A.E. Triggiano M.A. Hux J.A. Pham C.D. Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells Mol. Ther. 2017 10.1016/j.ymthe.2017.02.005 28237835 PMC5383629 · DOI
  53. [54]Roth T.L. Puig-saus C. Yu R. Shifrut E. Carnevale J. Li J. Hiatt J. Saco J. Krystofinski P. Li H. Repromming human T cell function and specificity with non-viral genome targeting Nature 2018 10.1038/s41586-018-0326-5 29995861 PMC6239417 · DOI · Paper page
  54. [55]Schober K. Müller T.R. Busch D.H. Orthotopic T-Cell Receptor Replacement-An “Enabler” for TCR-Based Therapies Cells 2020 9 1367 10.3390/cells9061367 PMC7348731 32492858 · DOI
  55. [56]Abate-Daga D. Hanada K.I. Davis J.L. Yang J.C. Rosenberg S.A. Morgan R.A. Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes Blood 2013 122 1399 1410 10.1182/blood-2013-04-495531 23861247 PMC3750338 · DOI
  56. [57]Datar I. Sanmamed M.F. Wang J. Henick B.S. Choi J. Badri T. Dong W. Mani N. Toki M. Mejías L.D. Expression analysis and significance of PD-1, LAG-3, and TIM-3 in human non-small cell lung cancer using spatially resolved and multiparametric single-cell analysis Clin. Cancer Res. 2019 25 4663 4673 10.1158/1078-0432.CCR-18-4142 31053602 PMC7444693 · DOI
  57. [58]Li X. Wang R. Fan P. Yao X. Qin L. Peng Y. Ma M. Asley N. Chang X. Feng Y. A comprehensive analysis of key immune checkpoint receptors on tumor-infiltrating t cells from multiple types of cancer Front. Oncol. 2019 9 10.3389/fonc.2019.01066 PMC6823747 31709176 · DOI
  58. [59]Moon E.K. Ranganathan R. Eruslanov E. Kim S. Newick K. O’Brien S. Lo A. Liu X. Zhao Y. Albelda S.M. Blockade of programmed death 1 augments the ability of human T cells engineered to target NY-ESO-1 to control tumor growth after adoptive transfer Clin. Cancer Res. 2016 22 436 447 10.1158/1078-0432.CCR-15-1070 26324743 PMC4715990 · DOI
  59. [60]Cherkassky L. Morello A. Villena-Vargas J. Feng Y. Dimitrov D.S. Jones D.R. Sadelain M. Adusumilli P.S. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition J. Clin. Investig. 2016 126 3130 3144 10.1172/JCI83092 27454297 PMC4966328 · DOI
  60. [62]Su S. Hu B. Shao J. Shen B. Du J. Du Y. Zhou J. Yu L. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients Nat. Publ. Gr. 2016 1 14 10.1038/srep20070 PMC4730182 26818188 · DOI
  61. [63]Menger L. Sledzinska A. Bergerhoff K. Varga F.A. Smith J. Poirot L. Pule M. Hererro J. Peggs K.S. Quezada S.A. TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors Cancer Res. 2016 76 2087 2093 10.1158/0008-5472.CAN-15-3352 27197251 · DOI
  62. [64]Choi B.D. Yu X. Castano A.P. Darr H. Henderson D.B. Bouffard A.A. Larson R.C. Scarfò I. Bailey S.R. Gerhard G.M. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma J. Immunother. Cancer 2019 7 1 8 10.1186/s40425-019-0806-7 31727131 PMC6857271 · DOI
  63. [65]McGowan E. Lin Q. Ma G. Yin H. Chen S. Lin Y. PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges Biomed. Pharmacother. 2020 121 109625 10.1016/j.biopha.2019.109625 31733578 · DOI
  64. [66]Rapoport A.P. Stadtmauer E.A. Binder-Scholl G.K. Goloubeva O. Vogl D.T. Lacey S.F. Badros A.Z. Garfall A. Weiss B. Finklestein J. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma Nat. Med. 2015 21 914 921 10.1038/nm.3910 26193344 PMC4529359 · DOI
  65. [67]Ghosh D. Venkataramani P. Nandi S. Bhattacharjee S. CRISPR–Cas9 a boon or bane: The bumpy road ahead to cancer therapeutics Cancer Cell Int. 2019 1 10 10.1186/s12935-019-0726-0 30636933 PMC6325665 · DOI
  66. [68]Weber J. Öllinger R. Friedrich M. Ehmer U. Barenboim M. Steiger K. Heid I. CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice Proc. Natl. Acad. Sci. USA 2015 112 10.1073/pnas.1512392112 PMC4653208 26508638 · DOI
  67. [69]Li J. Hong S. Chen W. Zuo E. Yang H. Advances in detecting and reducing off-target effects generated by CRISPR-mediated genome editing J. Genet. Genom. 2019 46 513 521 10.1016/j.jgg.2019.11.002 31911131 · DOI
  68. [71]Slaymaker I.M. Gao L. Zetsche B. Scott D.A. Yan W.X. Zhang F. Rationally engineered Cas9 nucleases with improved specificity Science 2016 351 84 88 10.1126/science.aad5227 26628643 PMC4714946 · DOI · Paper page
  69. [72]Kleinstiver B.P. Pattanayak V. Prew M.S. Tsai S.Q. Nguyen N.T. Zheng Z. Joung J.K. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects Nature 2016 529 490 495 10.1038/nature16526 26735016 PMC4851738 · DOI · Paper page
  70. [74]Lu Y. Xue J. Deng T. Zhou X. Yu K. Deng L. Huang M. Yi X. Liang M. Wang Y. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer Nat. Med. 2020 26 732 740 10.1038/s41591-020-0840-5 32341578 · DOI
  71. [75]Gaudelli N.M. Komor A.C. Rees H.A. Packer M.S. Badran A.H. Bryson D.I. Liu D.R. Programmable base editing of A-T to G-C in genomic DNA without DNA cleavage Nature 2017 551 464 471 10.1038/nature24644 29160308 PMC5726555 · DOI · Paper page
  72. [76]Webber B.R. Lonetree C. Kluesner M.G. Johnson M.J. Pomeroy E.J. Diers M.D. Lahr W.S. Draper G.M. Slipek N.J. Smeester B.S. Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors Nat. Commun. 2019 10 10.1038/s41467-019-13007-6 PMC6864045 31745080 · DOI · Paper page
  73. [77]Dwyer C.J. Knochelmann H.M. Smith A.S. Wyatt M.M. Rivera G.O.R. Arhontoulis D.C. Bartee E. Li Z. Rubinstein M.P. Paulos C.M. Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines Front. Immmunol. 2019 10 1 18 10.3389/fimmu.2019.00263 30842774 PMC6391336 · DOI
  74. [78]White D.E. Rosenberg S.A. Trends in the Safety of High Dose Bolus Interleukin-2 Administration in Patients with Metastatic Cancer Cancer 1998 2 797 805 9708948
  75. [79]Tang A. Harding F. The challenges and molecular approaches surrounding interleukin-2-based therapeutics in cancer Cytokine X 2019 1 100001 10.1016/j.cytox.2018.100001 · DOI
  76. [80]Liu K. Rosenberg S.A. Transduction of an IL-2 Gene into Human Melanoma-Reactive Lymphocytes Results in Their Continued Growth in the Absence of Exogenous IL-2 and Maintenance of Specific Antitumor Activity J. Immunol. 2001 10.4049/jimmunol.167.11.6356 PMC2430884 11714800 · DOI
  77. [81]Heemskerk B. Liu K. Dudley M.E. Johnson L.A. Kaiser A. Downey S. Zheng Z. Shelton T.E. Matsuda K. Robbins P.F. Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2 Hum. Gene Ther. 2008 19 496 510 10.1089/hum.2007.0171 18444786 PMC2656366 · DOI
  78. [82]Kunert A. Chmielewski M. Wijers R. Berrevoets C. Abken H. Debets R. Intra-tumoral production of IL18, but not IL12, by TCR-engineered T cells is non-toxic and counteracts immune evasion of solid tumors Oncoimmunology 2018 7 1 12 10.1080/2162402X.2017.1378842 29296541 PMC5739571 · DOI
  79. [83]Alsaieedi A. Holler A. Velica P. Bendle G. Stauss H.J. Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells Oncoimmunology 2019 8 1 11 10.1080/2162402X.2018.1542917 30723575 PMC6350686 · DOI
  80. [84]Zhang L. Davies J.S. Serna C. Yu Z. Restifo N.P. Rosenberg S.A. Morgan R.A. Hinrichs C.S. Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models J. Immunother. Cancer 2019 1 12 10.1136/jitc-2019-000210 31959727 PMC7057422 · DOI
  81. [85]Zhang L. Morgan R.A. Beane J.D. Zheng Z. Dudley M.E. Kassim S.H. Nahvi A.V. Ngo L.T. Sherry R.M. Phan G.Q. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma Clin. Cancer Res. 2015 21 2278 2288 10.1158/1078-0432.CCR-14-2085 25695689 PMC4433819 · DOI
  82. [86]Koneru M. O’Cearbhaill R. Pendharkar S. Spriggs D.R. Brentjens R.J. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer J. Transl. Med. 2015 13 1 11 10.1186/s12967-015-0460-x 25890361 PMC4438636 · DOI
  83. [87]Gonzales C. Yoshihara H.A.I. Dilek N. Leignadier J. Irving M. Mieville P. Helm L. Michielin O. Schwitter J. In-vivo detection and tracking of T cells in various organs in a melanoma tumor model by 19F-fluorine MRS/MRI PLoS ONE 2016 11 1 18 10.1371/journal.pone.0164557 PMC5063406 27736925 · DOI
  84. [88]Boschi F. De Sanctis F. Ugel S. Spinelli A.E. T-cell tracking using Cerenkov and radioluminescence imaging J. Biophotonics 2018 11 1 11 10.1002/jbio.201800093 29770603 · DOI
  85. [89]Nagarsheth N. Wicha M.S. Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy Nat. Publ. Gr. 2017 17 559 572 10.1038/nri.2017.49 PMC5731833 28555670 · DOI
  86. [90]Bronger H. Singer J. Windmu C. Reuning U. Zech D. Delbridge C. CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer Br. J. Cancer 2016 553 563 10.1038/bjc.2016.172 27490802 PMC4997538 · DOI
  87. [91]Curiel T.J. Coukos G. Zou L. Alvarez X. Cheng P. Mottram P. Evdemon-Hogan M. Conejo-Garcia J.R. Zhang L. Burow M. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival Nat. Med. 2004 10 942 949 10.1038/nm1093 15322536 · DOI · Paper page
  88. [92]Kershaw M.H. Wang G. Westwood J.A. Pachynski R.K. Tiffany H.L. Marincola F.M. Wang E. Young H.A. Murphy P.M. Hwu P. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2 Hum. Gene Ther. 2002 13 1971 1980 10.1089/10430340260355374 12427307 · DOI
  89. [93]Idorn M. Skadborg S.K. Kellermann L. Halldórsdóttir H.R. Holmen Olofsson G. Met Ö. Thor Straten P. Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model Oncoimmunology 2018 7 10.1080/2162402X.2018.1450715 30221044 PMC6136860 · DOI
  90. [94]Jin L. Tao H. Karachi A. Long Y. Hou A.Y. Na M. Dyson K.A. Grippin A.J. Deleyrolle L.P. Zhang W. CXCR1- or CXCR2-modified CAR T cells co-opt IL- 8 for maximal antitumor efficacy in solid tumors Nat. Commun. 2019 1 13 10.1038/s41467-019-11869-4 31488817 PMC6728370 · DOI
  91. [95]Bremnes R.M. Dønnem T. Al-Saad S. Al-Shibli K. Andersen S. Sirera R. Camps C. Marinez I. Busund L.T. The role of tumor stroma in cancer progression and prognosis: Emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer J. Thorac. Oncol. 2011 6 209 217 10.1097/JTO.0b013e3181f8a1bd 21107292 · DOI · Paper page
  92. [96]Liu R. Li H. Liu L. Yu J. Ren X. Fibroblast activation protein: A potential therapeutic target in cancer Cancer Biol. Ther. 2012 4047 10.4161/cbt.13.3.18696 22236832 · DOI
  93. [97]Wang L.S. Lo A. Scholler J. Sun J. Majumdar R.S. Kapoor V. Antzis M. Cotner C.E. Johnson L.A. Durham A.C. Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity Cancer Immunol. Res. 2014 2 154 167 10.1158/2326-6066.CIR-13-0027 24778279 PMC4007316 · DOI · Paper page
  94. [98]Mpekris F. Voutouri C. Baish J.W. Duda D.G. Munn L.L. Combining microenvironment normalization strategies to improve cancer immunotherapy Proc. Natl. Acad. Sci. USA 2020 117 10.1073/pnas.1919764117 PMC7035612 32015113 · DOI
  95. [99]Lanitis E. Irving M. Coukos G. Targeting the tumor vasculature to enhance T cell activity Curr. Opin. Immunol. 2015 33 55 63 10.1016/j.coi.2015.01.011 25665467 PMC4896929 · DOI
  96. [100]Chinnasamy D. Yu Z. Theoret M.R. Zhao Y. Shrimali R.K. Morgan R.A. Feldman S.A. Restifo N.P. Rosenberg S.A. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice J. Clin. Investig. 2010 120 3953 3968 10.1172/JCI43490 20978347 PMC2964987 · DOI
  97. [101]Chinnasamy D. Tran E. Yu Z. Morgan R.A. Restifo N.P. Rosenberg S.A. Simultaneous targeting of tumor antigens and the tumor vasculature using t lymphocyte transfer synergize to induce regression of established tumors in mice Cancer Res. 2013 73 3371 3380 10.1158/0008-5472.CAN-12-3913 23633494 PMC3686092 · DOI
  98. [102]Casucci M. Di Robilant B.N. Falcone L. Camisa B. Norelli M. Genovese P. Gentner B. Gullotta F. Ponzoni M. Bernardi M. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma Blood 2013 122 3461 3472 10.1182/blood-2013-04-493361 24016461 · DOI
  99. [103]Porcellini S. Asperti C. Corna S. Cicoria E. Valtolina V. Stornaiuolo A. Valentinis B. Bordignon C. Traversari C. CAR T Cells Redirected to CD44v6 Control Tumor Growth in Lung and Ovary Adenocarcinoma Bearing Mice Front. Immunol. 2020 11 1 14 10.3389/fimmu.2020.00099 32117253 PMC7010926 · DOI
  100. [104]Murty S. Labanieh L. Murty T. Gowrishankar G. Haywood T. Alam I.S. Beinat C. Robinson E. Aalipour A. Klysz D.D. PET reporter gene imaging and ganciclovir-mediated ablation of chimeric antigen receptor T-cells in solid tumors Cancer Res. 2020 10.1158/0008-5472.CAN-19-3579 32958548 · DOI
  101. [105]Tiberghien P. Ferrand C. Lioure B. Milpied N. Angonin R. Deconinck E. Certoux J.M. Robinet E. Saas P. Petracca B. Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft Blood 2001 97 63 72 10.1182/blood.V97.1.63 11133743 · DOI
  102. [106]Straathof K.C. Pulè M.A. Yotnda P. Dotti G. Vanin E.F. Brenner M.K. Heslop H.E. Spencer D.M. Rooney C.M. An inducible caspase 9 safety switch for T-cell therapy Blood 2005 105 4247 4254 10.1182/blood-2004-11-4564 15728125 PMC1895037 · DOI
  103. [107]Di Stasi A. Tey S.K. Dotti G. Fujita Y. Kennedy-Nasser A. Martinez C. Straathof K. Liu E. Durett A.G. Grilley B. Inducible apoptosis as a safety switch for adoptive cell therapy N. Engl. J. Med. 2011 365 1673 1683 10.1056/NEJMoa1106152 22047558 PMC3236370 · DOI · Paper page
  104. [108]Stavrou M. Philip B. Traynor-White C. Davis C.G. Onuoha S. Cordoba S. Thomas S. Pule M. A Rapamycin-Activated Caspase 9-Based Suicide Gene Mol. Ther. 2018 26 1266 1276 10.1016/j.ymthe.2018.03.001 29661681 PMC5993966 · DOI

Authors
Lo Presti, V., Buitenwerf, F., van Til, N. P., & Nierkens, S.
Affiliations
  • Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
  • University Medical Center Utrecht (NL)
ORCID
Venue
Vaccines
Publisher
MDPI AG
Published
2020-12-03
Volume
8
Issue
4
Pages
733
ISSN
2076-393X (ISSN-L)
DOI
10.3390/vaccines8040733
PMC
PMC7761868
OpenAlex
W3107298471
Cited by
14
References
112
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 5
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Vaccines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
KWF Kankerbestrijding (10474)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
T cell engineering, solid tumors, genome editing, tumor microenvironment, tumor stroma, tumor heterogeneity, on-target off-tumor toxicity, safety switch, tumor-associated antigens, adoptive T cell therapy, clinical trials

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review