Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors

References

• Baeuerle PA, Ding J, Patel E, Thorausch N, Horton H, Gierut J, Scarfo I, Choudhary R, Kiner O, Krishnamurthy J, et al. Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response. Nat Commun. 2019;10(1):2087. doi:10.1038/s41467-019-10097-0.
   PubMed Web of Science ®Google Scholar
• Helsen CW, Hammill, J. A., Lau, V. W., Mwawasi, K. A., Afsahi, A., Bezverbnaya, K. & Bramson, J. L. The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nat Commun. 2018;9:3049. doi:10.1038/s41467-018-05395-y.
   PubMed Web of Science ®Google Scholar
• Xu Y, Morales AJ, Cargill MJ, Towlerton AMH, Coffey DG, Warren EH, Tykodi SS. Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma. Cancer Immunol Immunother. 2019;68:1979–11. doi:10.1007/s00262-019-02419-4.
   PubMed Web of Science ®Google Scholar
• Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020;396:839–852. doi:10.1016/S0140-6736(20)31366-0.
   PubMed Web of Science ®Google Scholar
• Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B. al.CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24:20–28. doi:10.1038/nm.4441.
   PubMed Web of Science ®Google Scholar
• Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, Bleakley M, Brown C, Mgebroff S, Kelly-Spratt KS, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129:3322–3331. doi:10.1182/blood-2017-02-769208.
   PubMed Web of Science ®Google Scholar
• Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20:31–42. doi:10.1016/S1470-2045(18)30864-7.
   PubMed Web of Science ®Google Scholar
• Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125:4017–4023. doi:10.1182/blood-2014-12-580068.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole O, Lin Y, Braunschweig I, Hill BT, Timmerman J, et al. 2-year follow-up and high-risk subset analysis of zuma-1, the pivotal study of axicabtagene ciloleucel (axi-cel) in patients with refractory large B cell lymphoma. Biology of Blood and Marrow Transplantation. 2019;25:S65. doi:10.1016/j.bbmt.2018.12.148.
   Web of Science ®Google Scholar
• Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res. 2014;74(11):2907–2912. doi:10.1158/0008-5472.CAN-14-0337.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Haas, A. R., Maus, M. V., Torigian, D. A., Soulen, M. C., Plesa, G. & June, C. H. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2:112–120. doi:10.1158/2326-6066.CIR-13-0170.
   PubMed Web of Science ®Google Scholar
• Haas AR, Tanyi JL, O’Hara MH, Gladney WL, Lacey SF, Torigian DA, Soulen MC, Tian L, McGarvey M, Nelson AM, et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol Ther. 2019;27(11):1919–1929. doi:10.1016/j.ymthe.2019.07.015.
   PubMed Web of Science ®Google Scholar
• Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25(9):1341–1355. doi:10.1038/s41591-019-0564-6.
   PubMed Web of Science ®Google Scholar
• O’Rourke DM, Nasrallah, M. P., Desai, A., Melenhorst, J. J., Mansfield, K., Morrissette, J. J. & Maus, M. V. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9. doi:10.1126/scitranslmed.aaa0984
   PubMed Web of Science ®Google Scholar
• Whilding LM, Maher J. CAR T-cell immunotherapy: the path from the by-road to the freeway? Mol Oncol. 2015;9(10):1994–2018. doi:10.1016/j.molonc.2015.10.012.
   PubMed Web of Science ®Google Scholar
• Adusumilli PS, Zauderer MG, Rivière I, Solomon SB, Rusch VW, O’Cearbhaill RE, Zhu A, Cheema W, Chintala NK, Halton E, et al. A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discov. 2021;11(11):2748–2763. doi:10.1158/2159-8290.CD-21-0407.
   PubMed Web of Science ®Google Scholar
• Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, Varela-Rohena A, Haines KM, Heitjan DF, Albelda SM, et al. 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;106:3360–3365. doi:10.1073/pnas.0813101106.
   PubMed Web of Science ®Google Scholar
• Wagner J, Wickman E, DeRenzo C, Gottschalk S. CAR T cell therapy for solid tumors: bright future or dark reality? Mol Ther. 2020;28(11):2320–2339. doi:10.1016/j.ymthe.2020.09.015.
   PubMed Web of Science ®Google Scholar
• Delpoux A, Lai C-Y, Hedrick SM, Doedens AL. FOXO1 opposition of CD8 + T cell effector programming confers early memory properties and phenotypic diversity. Proc Natl Acad Sci U S A. 2017;114:E8865–E8874. doi:10.1073/pnas.1618916114.
   PubMed Web of Science ®Google Scholar
• Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJC, Hamieh M, Cunanan KM, Odak A, Gönen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017;543:113–117. doi:10.1038/nature21405.
   PubMed Web of Science ®Google Scholar
• Li W, Qiu S, Chen J, Jiang S, Chen W, Jiang J, Wang F, Si W, Shu Y, Wei P, et al. Chimeric antigen receptor designed to prevent ubiquitination and downregulation showed durable antitumor efficacy. Immunity. 2020;53(2):456–470. doi:10.1016/j.immuni.2020.07.011.
   PubMed Web of Science ®Google Scholar
• Liu D, Badeti S, Dotti G, Jiang J-G, Wang H, Dermody J, Soteropoulos P, Streck D, Birge RB, Liu C, et al. The role of immunological synapse in predicting the efficacy of Chimeric Antigen Receptor (CAR) immunotherapy. Cell Commun Signal. 2020;18(1):134. doi:10.1186/s12964-020-00617-7.
   PubMed Web of Science ®Google Scholar
• Davenport AJ, Cross RS, Watson KA, Liao Y, Shi W, Prince HM, Beavis PA, Trapani JA, Kershaw MH, Ritchie DS, et al. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity. Proc Natl Acad Sci U S A. 2018;115:E2068–E2076. doi:10.1073/pnas.1716266115.
   PubMed Web of Science ®Google Scholar
• Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, Jones DR, Sadelain M. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6:261ra151. doi:10.1126/scitranslmed.3010162.
   PubMed Web of Science ®Google Scholar
• Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018;36:346–351. doi:10.1038/nbt.4086.
   PubMed Web of Science ®Google Scholar
• Craddock JA, Lu A, Bear A, Pule M, Brenner MK, Rooney CM, Foster AE. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother. 2010;33:780–788. doi:10.1097/CJI.0b013e3181ee6675.
   PubMed Web of Science ®Google Scholar
• Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, Heslop HE, Brenner MK, Dotti G, Savoldo B, et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113:6392–6402. doi:10.1182/blood-2009-03-209650.
   PubMed Web of Science ®Google Scholar
• Moon EK, Carpenito C, Sun J, Wang LCS, Kapoor V, Predina J, Powell DJ, Riley JL, June CH, Albelda SM, et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin Cancer Res. 2011;17:4719–4730. doi:10.1158/1078-0432.CCR-11-0351.
   PubMed Web of Science ®Google Scholar
• Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra225. doi:10.1126/scitranslmed.3008226.
   Web of Science ®Google Scholar
• 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;3:95ra73. doi:10.1126/scitranslmed.3002842.
   PubMed Web of Science ®Google Scholar
• Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012;119:2709–2720. doi:10.1182/blood-2011-10-384388.
   PubMed Web of Science ®Google Scholar
• Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–528. doi:10.1016/S0140-6736(14)61403-3.
   PubMed Web of Science ®Google Scholar
• Hardy IR, Schamel WW, Baeuerle PA, Getts DR, Hofmeister R. Implications of T cell receptor biology on the development of new T cell therapies for cancer. Immunotherapy. 2020;12:89–103. doi:10.2217/imt-2019-0046.
   PubMed Web of Science ®Google Scholar
• Sugiura A, Rathmell JC. Metabolic barriers to T cell function in tumors. J Immunol. 2018;200:400–407. doi:10.4049/jimmunol.1701041.
   PubMed Web of Science ®Google Scholar
• Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, Roychoudhuri R, Palmer DC, Muranski P, Karoly ED, et al. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Invest. 2013;123:4479–4488. doi:10.1172/JCI69589.
   PubMed Web of Science ®Google Scholar
• Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, Werner MT, Huang AC, Alexander KA, Wu JE, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571:211–218. doi:10.1038/s41586-019-1325-x.
   PubMed Web of Science ®Google Scholar
• Meissner M, Reichert TE, Kunkel M, Gooding W, Whiteside TL, Ferrone S, Seliger B. Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin Cancer Res. 2005;11:2552–2560. doi:10.1158/1078-0432.CCR-04-2146.
   PubMed Web of Science ®Google Scholar
• Romero JM, Jiménez P, Cabrera T, Cózar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F. Coordinated downregulation of the antigen presentation machinery and HLA class I/beta 2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer. Int J Cancer. 2005;113:605–610. doi:10.1002/ijc.20499.
   PubMed Web of Science ®Google Scholar
• Seliger B, Ritz U, Abele R, Bock M, Tampé R, Sutter G, Drexler I, Huber C, Ferrone S. Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway. Cancer Res. 2001;61:8647–8650.
   PubMed Web of Science ®Google Scholar
• Hong DS, SciMentum SL, Tanyi J, MacMullen L, Jalbert L, Muzithras VP, Zikaras K, Cao L, O’Cearbhaill RE, Quintás-Cardama A, et al. Gavocabtagene autoleucel (gavo-cel, TC-210) dose escalation in refractory mesothelin-expressing solid tumors. Annals of Oncology. 2021;32:S829–S866. doi:10.1016/j.annonc.2021.08.1344.
   PubMed Web of Science ®Google Scholar
• DeTora L, Toroser D, Sykes A, Vanderlinden C, Plunkett FJ, Lane T, Hanekamp E, Dormer L, DiBiasi F, Bridges D, et al. Good Publication Practice (GPP) guidelines for company-sponsored biomedical research: 2022 update. Ann Intern Med. 2022;175:1298–1304. doi:10.7326/M22-1460.
   PubMed Web of Science ®Google Scholar