Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting

References

• Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377:2545–11. doi:10.1056/NEJMoa1708566.
   PubMed Web of Science ®Google Scholar
• Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–398. doi:10.1158/2159-8290.CD-12-0548.
   PubMed Web of Science ®Google Scholar
• Davila ML, Kloss CC, Gunset G, Sadelain M. CD19 CAR-targeted T cells induce long-term remission and B cell aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia. PLoS One. 2013;8:1–14. doi:10.1371/journal.pone.0061338.
   Web of Science ®Google Scholar
• June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73. doi:10.1056/NEJMra1706169.
   PubMed Web of Science ®Google Scholar
• June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359:1361–1365. doi:10.1126/science.aar6711.
   PubMed Web of Science ®Google Scholar
• Weinkove R, George P, Dasyam N, McLellan AD. Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations. Clin Transl Immunol. 2019;8. doi:10.1002/cti2.1049.
   PubMed Web of Science ®Google Scholar
• Mohty M, Gautier J, Malard F, Aljurf M, Bazarbachi A, Chabannon C, Kharfan-Dabaja MA, Savani BN, Huang H, Kenderian S, et al. CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Leukemia. 2019;2767–2778. doi:doi:10.1038/s41375-019-0615-5.
   PubMedGoogle Scholar
• Subklewe M, Von Bergwelt-Baildon M, Humpe A. Chimeric antigen receptor T cells: A race to revolutionize cancer therapy. Transfus Med Hemotherapy. 2019;46:15–24. doi:10.1159/000496870.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017;377:2531–2544. doi:10.1056/NEJMoa1707447.
   PubMed Web of Science ®Google Scholar
• Allen ES, Stroncek DF, Ren J, Eder AF, West KA, Fry TJ, Lee DW, Mackall CL, Conry-Cantilena C. Autologous lymphapheresis for the production of chimeric antigen receptor T cells. Transfusion. 2017;57(5):1133–1141. doi:10.1111/trf.14003.
   PubMed Web of Science ®Google Scholar
• You F, Wang Y, Jiang L, Zhu X, Chen D, Yuan L, An G, Meng H, Yang L. A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. Am J Cancer Res. 2019;9:64–78.
   PubMed Web of Science ®Google Scholar
• Ceppi F, Rivers J, Annesley C, Pinto N, Park JR, Lindgren C, Mgebroff S, Linn N, Delaney M, Gardner RA, et al. Lymphocyte apheresis for chimeric antigen receptor T-cell manufacturing in children and young adults with leukemia and neuroblastoma. Transfusion. 2018;58(6):1414–1420. doi:10.1111/trf.14569.
   PubMed Web of Science ®Google Scholar
• Mackall CL, Fleisher TA, Brown MR, Magrath IT, Shad AT, Horowitz ME, Wexler LH, Adde MA, McClure LL, Gress RE, et al. Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood. 1994;84(7):2221–2228. doi:10.1182/blood.V84.7.2221.2221.
   PubMed Web of Science ®Google Scholar
• Mackall CL. T-cell immunodeficiency following cytotoxic antineoplastic therapy: A review. Stem Cells. 2000;18:10–18. doi:10.1634/stemcells.18-1-10.
   PubMed Web of Science ®Google Scholar
• Verma R, Foster RE, Horgan K, Mounsey K, Nixon H, Smalle N, Hughes TA, Carter CR. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Breast Cancer Res. 2016;18(1):1–12. doi:10.1186/s13058-015-0669-x.
   PubMed Web of Science ®Google Scholar
• Feldmann A, Arndt C, Koristka S, Berndt N, Bergmann R, Bachmann MP. Conventional CARs versus modular CARs. Cancer Immunol Immunother. 2019;68:1713–1719. doi:10.1007/s00262-019-02399-5.
   PubMed Web of Science ®Google Scholar
• Bachmann M. The UniCAR system: A modular CAR T cell approach to improve the safety of CAR T cells. Immunol Lett. 2019;211:13–22.
   PubMed Web of Science ®Google Scholar
• Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16:7–19.
   PubMed Web of Science ®Google Scholar
• Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020;382:545–553. doi:10.1056/NEJMoa1910607.
   PubMed Web of Science ®Google Scholar
• Wang W, Jiang J, Wu C. CAR-NK for tumor immunotherapy: clinical transformation and future prospects. Cancer Lett. 2020;472:175–180. doi:10.1016/j.canlet.2019.11.033.
   PubMed Web of Science ®Google Scholar
• Rezvani K. Adoptive cell therapy using engineered natural killer cells. Bone Marrow Transplant. 2019;54:785–788. doi:10.1038/s41409-019-0601-6.
   PubMed Web of Science ®Google Scholar
• Shimasaki N, Fujisaki H, Cho D, Masselli M, Lockey T, Eldridge P, Leung W, Campana D. A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies. Cytotherapy. 2012;14:830–840. doi:10.3109/14653249.2012.671519.
   PubMed Web of Science ®Google Scholar
• Oelsner S, Wagner J, Friede ME, Pfirrmann V, Genßler S, Rettinger E, Buchholz CJ, Pfeifer H, Schubert R, Ottmann OG, et al. Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival. Int J Cancer. 2016;139:1799–1809. doi:10.1002/ijc.30217.
   PubMed Web of Science ®Google Scholar
• Boissel L, Betancur M, Wels WS, Tuncer H, Klingemann H. Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. Leuk Res. 2009;33:1255–1259. doi:10.1016/j.leukres.2008.11.024.
   PubMed Web of Science ®Google Scholar
• Sutlu T, Nyström S, Gilljam M, Stellan B, Applequist SE, Alici E. Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy. Hum Gene Ther. 2012;23:1090–1100.
   PubMed Web of Science ®Google Scholar
• Zhang C, Oberoi P, Oelsner S, Waldmann A, Lindner A, Tonn T, Wels WS. Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol. 2017;8:1–17. doi:10.3389/fimmu.2017.00533.
   PubMed Web of Science ®Google Scholar
• Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, et al. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019;3:1970–1980. doi:10.1182/bloodadvances.2018028332.
   PubMed Web of Science ®Google Scholar
• Nowakowska P, Romanski A, Miller N, Odendahl M, Bonig H, Zhang C, Seifried E, Wels WS, Tonn T. Clinical grade manufacturing of genetically modified, CAR-expressing NK-92 cells for the treatment of ErbB2-positive malignancies. Cancer Immunol Immunother. 2018;67:25–38. doi:10.1007/s00262-017-2055-2.
   PubMed Web of Science ®Google Scholar
• Merker M, Pfirrmann V, Oelsner S, Fulda S, Klingebiel T, Wels WS, Bader P, Rettinger E. Generation and characterization of ErbB2-CAR-engineered cytokine-induced killer cells for the treatment of high-risk soft tissue sarcoma in children. Oncotarget. 2017;8(39):66137–66153. doi:10.18632/oncotarget.19821.
   PubMedGoogle Scholar
• Jiang H, Zhang W, Shang P, Zhang H, Fu W, Ye F, Zeng T, Huang H, Zhang X, Sun W, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8:297–310. doi:10.1016/j.molonc.2013.12.001.
   PubMed Web of Science ®Google Scholar
• Klingemann HG, Wong E, Maki G. A cytotoxic NK-cell line (NK-92) for ex vivo purging of leukemia from blood. Biol Blood Marrow Transplant. 1996;2:68–75.
   PubMedGoogle Scholar
• Darowski D, Kobold S, Jost C, Klein C. Combining the best of two worlds: highly flexible chimeric antigen receptor adaptor molecules (CAR-adaptors) for the recruitment of chimeric antigen receptor T cells. MAbs. 2019;11(4):621–631. doi:10.1080/19420862.2019.1596511.
   PubMed Web of Science ®Google Scholar
• Minutolo NG, Hollander EE, Powell DJ. The emergence of universal immune receptor t cell therapy for cancer. Front Oncol. 2019;9. doi:10.3389/fonc.2019.00176.
   PubMed Web of Science ®Google Scholar
• Li X, Chen W. Mechanisms of failure of chimeric antigen receptor T-cell therapy. Curr Opin Hematol. 2019;26:427–433. doi:10.1097/MOH.0000000000000548.
   PubMed Web of Science ®Google Scholar
• Seitz CM, Schlegel P, Hau J, Krahl AC, Schroeder S, Bender G, Reiter S, Schleicher S, Schilbach K, Ebinger M, et al. Novel adapter chimeric antigen receptor (aCAR) T cells for temporally controllable targeting of single and multiple tumor antigens. Blood. 2017;130: 1912–1912.
   Web of Science ®Google Scholar
• Seitz CM, Kieble V, Illi C, Reiter S, Grote S, Mittelstaet J, Lock D, Kaiser A, Schleicher S, Handgretinger R, et al. Combinatorial targeting of multiple shared antigens by adapter-CAR-T cells (aCAR-Ts) allows target cell discrimination and specific lysis based on differential expression profiles. Blood. 2018;132: 4543–4543. doi:10.1182/blood-2018-99-115630.
   Web of Science ®Google Scholar
• Kaiser A, Mittelstaet J, Huppert V, Miltenyi S, Schlegel P, Seitz C, Lang P, Handgretinger R, Inventors; Miltenyi Biotec GmbH, assignee. Adapter chimeric antigen receptor expressing cells for targeting of multiple antigens - EP3315511A1. Eur Pat Off. 2018.
   Google Scholar
• Rezvani K, Rouce RH. The application of natural killer cell immunotherapy for the treatment of cancer. Front Immunol. 2015;6:578. doi:10.3389/fimmu.2015.00578.
   PubMed Web of Science ®Google Scholar
• Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for cancer immunotherapy. Mol Ther. 2017;25:1769–1781. doi:10.1016/j.ymthe.2017.06.012.
   PubMed Web of Science ®Google Scholar
• Klingemann H, Boissel L, Toneguzzo F. Natural killer cells for immunotherapy - advantages of the NK-92 cell line over blood NK cells. Front Immunol. 2016;7:91. doi:10.3389/fimmu.2016.00091.
   PubMed Web of Science ®Google Scholar
• Zhang J, Zheng H, Diao Y. Natural killer cells and current applications of chimeric antigen receptor-modified NK-92 cells in tumor immunotherapy. Int J Mol Sci. 2019;20:317.
   Web of Science ®Google Scholar
• Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15:1563–1570. doi:10.1016/j.jcyt.2013.06.017.
   PubMed Web of Science ®Google Scholar
• Tonn T, Becker S, Esser R, Schwabe D, Seifried E. Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematotherapy Stem Cell Res. 2001;10:535–544. doi:10.1089/15258160152509145.
   PubMed Web of Science ®Google Scholar
• Uherek C, Tonn T, Uherek B, Becker S, Schnierle B, Klingemann H-G, Wels W. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Blood. 2002;100:1265–1273. doi:10.1182/blood.V100.4.1265.h81602001265_1265_1273.
   PubMed Web of Science ®Google Scholar
• Maki G, Klingemann HG, Martinson JA, Tam YK. Factors regulating the cytotoxic activity of the human natural killer cell line, NK-92. J Hematotherapy Stem Cell Res. 2001;10:369–383. doi:10.1089/152581601750288975.
   PubMedGoogle Scholar
• Klingemann H. Are natural killer cells superior CAR drivers? Oncoimmunology. 2014;3:e28147. doi:10.4161/onci.28147.
   PubMed Web of Science ®Google Scholar
• Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a ‘safety switch’ to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014;5:235. doi:10.3389/fphar.2014.00235.
   PubMed Web of Science ®Google Scholar
• Oelsner S, Waldmann A, Billmeier A, Röder J, Lindner A, Ullrich E, Marschalek R, Dotti G, Jung G, Große‐Hovest L, et al. Genetically engineered CAR NK cells display selective cytotoxicity against FLT3-positive B-ALL and inhibit in vivo leukemia growth. Int J Cancer. 2019;145:1935–1945.
   PubMed Web of Science ®Google Scholar
• Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–448. doi:10.1056/NEJMoa1709866.
   PubMed Web of Science ®Google Scholar
• Topp MS, Gökbuget N, Zugmaier G, Degenhard E, Goebeler M-E, Klinger M, Neumann SA, Horst HA, Raff T, Viardot A, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120:5185–5187. doi:10.1182/blood-2012-07-441030.
   PubMed Web of Science ®Google Scholar
• Topp MS, Gökbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32:4134–4140. doi:10.1200/JCO.2014.56.3247.
   PubMed Web of Science ®Google Scholar
• Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517. doi:10.1056/NEJMoa1407222.
   PubMed Web of Science ®Google Scholar
• Mitwasi N, Feldmann A, Arndt C, Koristka S, Berndt N, Jureczek J, Loureiro LR, Bergmann R, Máthé D, Hegedüs N, et al. “UniCAR”-modified off-the-shelf NK-92 cells for targeting of GD2-expressing tumour cells. Sci Rep. 2020;10:1–16.
   PubMed Web of Science ®Google Scholar
• Lohmueller JJ, Ham JD, Kvorjak M, Finn OJ. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017. doi:10.1080/2162402X.2017.1368604.
   PubMed Web of Science ®Google Scholar
• Urbanska K, Lanitis E, Poussin M, Lynn RC, Gavin BP, Kelderman S, Yu J, Scholler N, Powell DJ. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res. 2012;72(7):1844–1852. doi:10.1158/0008-5472.CAN-11-3890.
   PubMed Web of Science ®Google Scholar