REVIEW
CAR T-cell therapy of solid tumors: promising approaches to modulating antitumor activity of CAR T cells
Russian Scientific Center for Roentgenoradiology, Moscow, Russia
Correspondence should be addressed: Yana Yu. Kiseleva
Profsoyuznaya, 86, Moscow, 117997; 89036728541 moc.liamg@avelesik.anay
Author contribution: Kiseleva YaYu analyzed the literature, prepared the draft of the manuscript, created the figures; Shishkin AM analyzed the literature and revised the manuscript; Ivanov AV analyzed the literature and revised the manuscript; Kulinich TM revised the manuscript; Bozhenko VK revised the manuscript.
- Palucka AK, Coussens LM. The Basis of Oncoimmunology. Cell. 2016; 164 (6): 1233–47. DOI: 10.1016/j.cell.2016.01.049. PubMed PMID: 26967289; PubMed Central PMCID: PMC4788788.
- Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. 2010; 116 (7): 1035–44. DOI: 10.1182/blood-2010-01-043737. PubMed PMID: 20439624; PubMed Central PMCID: PMC2938125.
- Klebanoff CA, Rosenberg SA, Restifo NP. Prospects for gene-engineered T cell immunotherapy for solid cancers. Nature medicine. 2016; 22 (1): 26–36. DOI: 10.1038/nm.4015. PubMed PMID: 26735408; PubMed Central PMCID: PMC6295670.
- Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016; 127 (26): 3312–20. DOI: 10.1182/ blood-2016-02-629063. PubMed PMID: 27207800; PubMed Central PMCID: PMC4929923.
- Liu B, Yan L, Zhou M. Target selection of CAR T cell therapy in accordance with the TME for solid tumors. American journal of cancer research. 2019; 9 (2): 228–41. PubMed PMID: 30906625; PubMed Central PMCID: PMC6405971.
- Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Molecular therapy oncolytics. 2016; (3): 16011. DOI: 10.1038/mto.2016.11. PubMed PMID: 27626062; PubMed Central PMCID: PMC5008265.
- Tahmasebi S, Elahi R, Esmaeilzadeh A. Solid Tumors Challenges and New Insights of CAR T Cell Engineering. Stem cell reviews and reports. 2019; 15 (5): 619–36. DOI: 10.1007/s12015-019- 09901-7. PubMed PMID: 31161552.
- Minutolo NG, Hollander EE, Powell DJ, Jr. The Emergence of Universal Immune Receptor T Cell Therapy for Cancer. Frontiers in oncology. 2019; (9): 176. DOI: 10.3389/fonc.2019.00176. PubMed PMID: 30984613; PubMed Central PMCID: PMC6448045.
- Stoiber S, Cadilha BL, Benmebarek MR, Lesch S, Endres S, Kobold S. Limitations in the Design of Chimeric Antigen Receptors for Cancer Therapy. Cells. 2019; 8 (5). DOI: 10.3390/ cells8050472. PubMed PMID: 31108883; PubMed Central PMCID: PMC6562702.
- Urbanska K, Lanitis E, Poussin M, Lynn RC, Gavin BP, Kelderman S, et al. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer research. 2012; 72 (7): 1844–52. DOI: 10.1158/0008-5472.CAN-11-3890. PubMed PMID: 22315351; PubMed Central PMCID: PMC3319867.
- Lohmueller JJ, Ham JD, Kvorjak M, Finn OJ. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017; 7 (1): e1368604. DOI: 10.1080/2162402X.2017.1368604. PubMed PMID: 29296519; PubMed Central PMCID: PMC5739565.
- Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R, Li Z, et al. Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Clinical cancer research: an official journal of the American Association for Cancer Research. 2012; 18 (23): 6436–45. DOI: 10.1158/1078-0432.CCR-12-1449. PubMed PMID: 23032741.
- Koristka S, Cartellieri M, Arndt C, Bippes CC, Feldmann A, Michalk I, et al. Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B. Journal of autoimmunity. 2013; (42): 105–16. DOI: 10.1016/j.jaut.2013.01.002. PubMed PMID: 23352111.
- Cartellieri M, Feldmann A, Koristka S, Arndt C, Loff S, Ehninger A, et al. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood cancer journal. 2016; 6 (8): e458. DOI: 10.1038/bcj.2016.61. PubMed PMID: 27518241; PubMed Central PMCID: PMC5022178 directed to CD33, La and the UniCAR platform technology. AE, SL and MC are employed by GEMoaB and CPT, respectively. The other authors declare no conflict of interest.
- Pishali Bejestani E, Cartellieri M, Bergmann R, Ehninger A, Loff S, Kramer M, et al. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model. Oncoimmunology. 2017; 6 (10): e1342909. DOI: 10.1080/2162402X.2017.1342909. PubMed PMID: 29123951; PubMed Central PMCID: PMC5665068.
- Feldmann A, Arndt C, Bergmann R, Loff S, Cartellieri M, Bachmann D, et al. Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology "UniCAR". Oncotarget. 2017; 8 (19): 31368–85. DOI: 10.18632/oncotarget.15572. PubMed PMID: 28404896; PubMed Central PMCID: PMC5458214.
- Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, et al. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113 (4): E459–68. DOI: 10.1073/pnas.1524155113. PubMed PMID: 26759369; PubMed Central PMCID: PMC4743815.
- Riddell SR, Sommermeyer D, Berger C, Liu LS, Balakrishnan A, Salter A, et al. Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. Cancer journal. 2014; 20 (2): 141–4. DOI: 10.1097/PPO.0000000000000036. PubMed PMID: 24667960; PubMed Central PMCID: PMC4149222.
- Cao Y, Rodgers DT, Du J, Ahmad I, Hampton EN, Ma JS, et al. Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer. Angewandte Chemie. 2016; 55 (26): 7520–4. DOI: 10.1002/anie.201601902. PubMed PMID: 27145250; PubMed Central PMCID: PMC5207029.
- Cho JH, Collins JJ, Wong WW. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Cell. 2018; 173 (6): 1426–38. DOI: 10.1016/j. cell.2018.03.038. PubMed PMID: 29706540; PubMed Central PMCID: PMC5984158.
- Scarfo I, Maus MV. Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment. Journal for immunotherapy of cancer. 2017; (5): 28. DOI: 10.1186/ s40425-017-0230-9. PubMed PMID: 28331617; PubMed Central PMCID: PMC5359946.
- Sioud M. Releasing the Immune System Brakes Using siRNAs Enhances Cancer Immunotherapy. Cancers. 2019; 11 (2). DOI: 10.3390/cancers11020176. PubMed PMID: 30717461.
- Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nature reviews Clinical oncology. 2016; 13 (8): 473–86. DOI: 10.1038/nrclinonc.2016.58. PubMed PMID: 27141885.
- Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and Transcriptomic Features of Response to Anti- PD-1 Therapy in Metastatic Melanoma. Cell. 2016; 165 (1): 35– 44. DOI: 10.1016/j.cell.2016.02.065. PubMed PMID: 26997480; PubMed Central PMCID: PMC4808437.
- Simon B, Harrer DC, Schuler-Thurner B, Schaft N, Schuler G, Dorrie J, et al. The siRNA-mediated downregulation of PD-1 alone or simultaneously with CTLA-4 shows enhanced in vitro CAR-T-cell functionality for further clinical development towards the potential use in immunotherapy of melanoma. Experimental dermatology. 2018; 27 (7): 769–78. DOI: 10.1111/exd.13678. PubMed PMID: 29704887.
- Martinez M, Moon EK. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Frontiers in immunology. 2019; (10): 128. DOI: 10.3389/fimmu.2019.00128. PubMed PMID: 30804938; PubMed Central PMCID: PMC6370640.
- Vivot A, Jacot J, Zeitoun JD, Ravaud P, Crequit P, Porcher R. Clinical benefit, price and approval characteristics of FDA-approved new drugs for treating advanced solid cancer, 2000– 2015. Annals of oncology: official journal of the European Society for Medical Oncology. 2017; 28 (5): 1111–6. DOI: 10.1093/ annonc/mdx053. PubMed PMID: 28453694.
- Medina PJ, Adams VR. PD-1 Pathway Inhibitors: Immuno- Oncology Agents for Restoring Antitumor Immune Responses. Pharmacotherapy. 2016; 36 (3): 317–34. DOI: 10.1002/phar.1714. PubMed PMID: 26822752; PubMed Central PMCID: PMC5071694.
- Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. The New England journal of medicine. 2015; 373 (1): 23–34. DOI: 10.1056/NEJMoa1504030. PubMed PMID: 26027431; PubMed Central PMCID: PMC5698905.
- Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. The New England journal of medicine. 2018; 378 (2): 158–68. DOI: 10.1056/NEJMra1703481. PubMed PMID: 29320654.
- Ren J, Liu X, Fang C, Jiang S, June CH, Zhao Y. Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition. Clinical cancer research: an official journal of the American Association for Cancer Research. 2017; 23 (9): 2255– 66. DOI: 10.1158/1078-0432.CCR-16-1300. PubMed PMID: 27815355; PubMed Central PMCID: PMC5413401.
- Yu Y, Wu H, Tang Z, Zang G. CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B patients. Cellular & molecular immunology. 2009; 6 (2): 123–7. DOI: 10.1038/cmi.2009.17. PubMed PMID: 19403062; PubMed Central PMCID: PMC4002649.
- Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, et al. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Scientific reports. 2017; 7 (1): 737. DOI: 10.1038/s41598-017- 00462-8. PubMed PMID: 28389661; PubMed Central PMCID: PMC5428439.
- Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, et al. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget. 2017; 8 (10): 17002–11. DOI: 10.18632/ oncotarget.15218. PubMed PMID: 28199983; PubMed Central PMCID: PMC5370017.
- Knochelmann HM, Smith AS, Dwyer CJ, Wyatt MM, Mehrotra S, Paulos CM. CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies. Frontiers in immunology. 2018; (9): 1740. DOI: 10.3389/fimmu.2018.01740. PubMed PMID: 30140266; PubMed Central PMCID: PMC6094980.
- Kerkar SP, Muranski P, Kaiser A, Boni A, Sanchez-Perez L, Yu Z, et al. Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts. Cancer research. 2010; 70 (17): 6725–34. DOI: 10.1158/0008-5472. CAN-10-0735. PubMed PMID: 20647327; PubMed Central PMCID: PMC2935308.
- Pegram HJ, Lee JC, Hayman EG, Imperato GH, Tedder TF, Sadelain M, et al. Tumor-targeted T cells modified to secrete IL12 eradicate systemic tumors without need for prior conditioning. Blood. 2012; 119 (18): 4133–41. DOI: 10.1182/ blood-2011-12-400044. PubMed PMID: 22354001; PubMed Central PMCID: PMC3359735.
- Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, et al. IL12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. The Journal of clinical investigation. 2011; 121 (12): 4746–57. DOI: 10.1172/JCI58814. PubMed PMID: 22056381; PubMed Central PMCID: PMC3226001.
- Zhang L, Morgan RA, Beane JD, Zheng Z, Dudley ME, Kassim SH, et al. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clinical cancer research: an official journal of the American Association for Cancer Research. 2015; 21 (10): 2278–88. DOI: 10.1158/1078-0432.CCR-14-2085. PubMed PMID: 25695689; PubMed Central PMCID: PMC4433819.
- 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. 2017; 7 (1): e1378842. DOI: 10.1080/2162402X.2017.1378842. PubMed PMID: 29296541; PubMed Central PMCID: PMC5739571.
- Alsaieedi A, Holler A, Velica P, Bendle G, Stauss HJ. Safety and efficacy of Tet-regulated IL12 expression in cancer-specific T cells. Oncoimmunology. 2019; 8 (3): 1542917. DOI: 10.1080/2162402X.2018.1542917. PubMed PMID: 30723575; PubMed Central PMCID: PMC6350686.
- Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/ leukemia effects and safety. Leukemia. 2010; 24 (6): 1160–70. DOI: 10.1038/leu.2010.75. PubMed PMID: 20428207; PubMed Central PMCID: PMC2888148.
- Krenciute G, Prinzing BL, Yi Z, Wu MF, Liu H, Dotti G, et al. Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Ralpha2-CAR T Cells but Results in Antigen Loss Variants. Cancer immunology research. 2017; 5 (7): 571–81. DOI: 10.1158/2326-6066.CIR-16-0376. PubMed PMID: 28550091; PubMed Central PMCID: PMC5746871.
- Hu B, Ren J, Luo Y, Keith B, Young RM, Scholler J, et al. Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL18. Cell reports. 2017; 20 (13): 3025–33. DOI: 10.1016/j.celrep.2017.09.002. PubMed PMID: 28954221; PubMed Central PMCID: PMC6002762.
- Chmielewski M, Abken H. CAR T Cells Releasing IL18 Convert to T-Bet(high) FoxO1(low) Effectors that Exhibit Augmented Activity against Advanced Solid Tumors. Cell reports. 2017; 21 (11): 3205–19. DOI: 10.1016/j.celrep.2017.11.063. PubMed PMID: 29241547.