CD46 and CD59 inhibitors enhance complement-dependent cytotoxicity of anti-CD38 monoclonal antibodies daratumumab and isatuximab in multiple myeloma and other B-cell malignancy cells

References

• Kegyes D, Gulei D, Drula R, Cenariu D, Tigu B, Dima D, Tanase A, Badelita S, Buzoianu AD, Ciurea S, et al. Proteasome inhibition in combination with immunotherapies: state-of-the-art in multiple myeloma. Blood Rev. 2023;61:101100. doi:10.1016/j.blre.2023.101100.
   PubMed Web of Science ®Google Scholar
• Dhillon S. Isatuximab: First Approval. Drugs. 2020;80(9):905–11. doi:10.1007/s40265-020-01311-1.
   PubMed Web of Science ®Google Scholar
• Marlein CR, Piddock RE, Mistry JJ, Zaitseva L, Hellmich C, Horton RH, Zhou Z, Auger MJ, Bowles KM, Rushworth SA. CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Res. 2019;79(9):2285–2297. doi:10.1158/0008-5472.CAN-18-0773.
   PubMed Web of Science ®Google Scholar
• Costa F, Dalla Palma B, Giuliani N. CD38 expression by Myeloma cells and its role in the context of bone marrow microenvironment: modulation by therapeutic agents. Cells. 2019;8(12):1632. doi:10.3390/cells8121632.
   PubMed Web of Science ®Google Scholar
• Stevenson FK, Bell AJ, Cusack R, Hamblin TJ, Slade CJ, Spellerberg MB, Stevenson GT. Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. Blood. 1991;77(5):1071–1079. doi:10.1182/blood.V77.5.1071.1071.
   PubMed Web of Science ®Google Scholar
• Konen JM, Fradette JJ, Gibbons DL. The good, the bad and the unknown of CD38 in the metabolic microenvironment and immune cell functionality of solid tumors. Cells. 2019;9(1):52. doi:10.3390/cells9010052.
   PubMed Web of Science ®Google Scholar
• Mistry JJ, Moore JA, Kumar P, Marlein CR, Hellmich C, Pillinger G, Jibril A, Di Palma F, Collins A, Bowles KM, et al. Daratumumab inhibits acute myeloid leukaemia metabolic capacity by blocking mitochondrial transfer from mesenchymal stromal cells. Haematologica. 2021;106(2):589–592. doi:10.3324/haematol.2019.242974.
   PubMed Web of Science ®Google Scholar
• Rajan AM, Kumar S. New investigational drugs with single-agent activity in multiple myeloma. Blood Cancer J. 2016;6(7):e451. doi:10.1038/bcj.2016.53.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375(14):1319–1331. doi:10.1056/NEJMoa1607751.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375(8):754–766. doi:10.1056/NEJMoa1606038.
   PubMed Web of Science ®Google Scholar
• Kikuchi T, Tsukada N, Nomura M, Kasuya Y, Oda Y, Sato K, Takei T, Ogura M, Abe Y, Suzuki K, et al. Real-world clinical outcomes in patients with multiple myeloma treated with isatuximab after daratumumab treatment. Ann Hematol. 2023;102(6):1477–1483. doi:10.1007/s00277-023-05218-1.
   PubMed Web of Science ®Google Scholar
• Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, Gupta R, Varnado W, Fiala MA, Chhabra S, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33(9):2266–2275. doi:10.1038/s41375-019-0435-7.
   PubMed Web of Science ®Google Scholar
• Park SS, Min Byun J, Yoon SS, Kim K, Jung SH, Lee JJ, Min CK. Daratumumab monotherapy for relapsed/refractory multiple myeloma, focussed on clinical trial-unfit patients and subsequent therapy. Br J Haematol. 2021;193(1):101–112. doi:10.1111/bjh.17071.
   PubMed Web of Science ®Google Scholar
• Melis JP, Strumane K, Ruuls SR, Beurskens FJ, Schuurman J, Parren PW. Complement in therapy and disease: regulating the complement system with antibody-based therapeutics. Mol Immunol. 2015;67(2):117–130. doi:10.1016/j.molimm.2015.01.028.
   PubMed Web of Science ®Google Scholar
• Meyer S, Leusen JH, Boross P. Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer. MAbs. 2014;6(5):1133–1144. doi:10.4161/mabs.29670.
   PubMed Web of Science ®Google Scholar
• Riley-Vargas RC, Gill DB, Kemper C, Liszewski MK, Atkinson JP. CD46: expanding beyond complement regulation. Trends Immunol. 2004;25(9):496–503. doi:10.1016/j.it.2004.07.004.
   PubMed Web of Science ®Google Scholar
• Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S. Defining the CD59-C9 binding interaction. J Biol Chem. 2006;281(37):27398–27404. doi:10.1074/jbc.M603690200.
   PubMed Web of Science ®Google Scholar
• Juhl H, Helmig F, Baltzer K, Kalthoff H, Henne-Bruns D, Kremer B. Frequent expression of complement resistance factors CD46, CD55, and CD59 on gastrointestinal cancer cells limits the therapeutic potential of monoclonal antibody 17-1A. J Surg Oncol. 1997;64:222–230. doi:10.1002/(sici)1096-9098(199703)64:3<222:aid-jso9>3.0.co;2-c.
   PubMed Web of Science ®Google Scholar
• Bjorge L, Hakulinen J, Wahlstrom T, Matre R, Meri S. Complement-regulatory proteins in ovarian malignancies. Int J Cancer. 1997;70:14–25. doi:10.1002/(sici)1097-0215(19970106)70:1<14:aid-ijc3>3.0.co;2-9.
   PubMed Web of Science ®Google Scholar
• Jarvis GA, Li J, Hakulinen J, Brady KA, Nordling S, Dahiya R, Meri S. Expression and function of the complement membrane attack complex inhibitor protectin (CD59) in human prostate cancer. Int J Cancer. 1997;71:1049–1055. doi:10.1002/(sici)1097-0215(19970611)71:6<1049:aid-ijc22>3.0.co;2-7.
   PubMed Web of Science ®Google Scholar
• Hakulinen J, Meri S. Expression and function of the complement membrane attack complex inhibitor protectin (CD59) on human breast cancer cells. Lab Invest. 1994;71(6):820–827.
   PubMed Web of Science ®Google Scholar
• Golay J, Lazzari M, Facchinetti V, Bernasconi S, Borleri G, Barbui T, Rambaldi A, Introna M. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood. 2001;98(12):3383–3389. doi:10.1182/blood.v98.12.3383.
   PubMed Web of Science ®Google Scholar
• Carter D, Lieber A. Protein engineering to target complement evasion in cancer. FEBS Lett. 2014;588(2):334–340. doi:10.1016/j.febslet.2013.11.007.
   PubMed Web of Science ®Google Scholar
• Ong HT, Timm MM, Greipp PR, Witzig TE, Dispenzieri A, Russell SJ, Peng KW. Oncolytic measles virus targets high CD46 expression on multiple myeloma cells. Exp Hematol. 2006;34(6):713–720. doi:10.1016/j.exphem.2006.03.002. S0301-472X(06)00137-8 [pii].
   PubMed Web of Science ®Google Scholar
• Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128(7):959–970. doi:10.1182/blood-2016-03-703439.
   PubMed Web of Science ®Google Scholar
• Zhu C, Song Z, Wang A, Srinivasan S, Yang G, Greco R, Theilhaber J, Shehu E, Wu L, Yang ZY, et al. Isatuximab acts through fc-dependent, independent, and direct pathways to kill multiple myeloma cells. Front Immunol. 2020;11:1771. doi:10.3389/fimmu.2020.01771.
   PubMed Web of Science ®Google Scholar
• Gaggar A, Shayakhmetov D, Lieber A. CD46 is a cellular receptor for group B adenoviruses. Nat Med. 2003;9(11):1408–1412. doi:10.1038/nm952.
   PubMed Web of Science ®Google Scholar
• Wang H, Liu Y, Li ZY, Fan X, Hemminki A, Lieber A. A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy. Blood. 2010;115(3):592–600. doi:10.1182/blood-2009-05-222463. blood-2009-05-222463 [pii].
   PubMed Web of Science ®Google Scholar
• Beyer I, Cao H, Persson J, Wang H, Liu Y, Yumul R, Li Z, Woodle D, Manger R, Gough M, et al. Transient removal of CD46 is safe and increases B-cell depletion by rituximab in CD46 transgenic mice and macaques. Mol Ther. 2013;21(2):291–299. doi:10.1038/mt.2012.212.
   PubMed Web of Science ®Google Scholar
• Richter M, Yumul R, Saydaminova K, Wang H, Gough M, Baldessari A, Cattaneo R, Lee F, Wang CH, Jang H, et al. Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic. Mol Ther Methods Clin Dev. 2016;5:16013. doi:10.1038/mtm.2016.13.
   PubMedGoogle Scholar
• Hu W, Yu Q, Hu N, Byrd D, Amet T, Shikuma C, Shiramizu B, Halperin JA, Qin X. A high-affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: implications for treatment of HIV-1/AIDS. J Immunol. 2010;184(1):359–368. doi:10.4049/jimmunol.0902278.
   PubMed Web of Science ®Google Scholar
• Cai B, Xie S, Liu F, Simone LC, Caplan S, Qin X, Naslavsky N. Rapid degradation of the complement regulator, CD59, by a novel inhibitor. J Biol Chem. 2014. 289:12109–12125. doi:10.1074/jbc.M113.547083.
   PubMed Web of Science ®Google Scholar
• Ge X, Wu L, Hu W, Fernandes S, Wang C, Li X, Brown JR, Qin X. rILYd4, a human CD59 inhibitor, enhances complement-dependent cytotoxicity of ofatumumab against rituximab-resistant B-cell lymphoma cells and chronic lymphocytic leukemia. Clin Cancer Res. 2011. 17:6702–6711. doi:10.1158/1078-0432.CCR-11-0647.
   PubMed Web of Science ®Google Scholar
• van de Donk N, Usmani SZ. CD38 antibodies in multiple myeloma: mechanisms of action and modes of resistance. Front Immunol. 2018. 9:2134. doi:10.3389/fimmu.2018.02134.
   PubMed Web of Science ®Google Scholar
• Nijhof IS, Groen RW, Lokhorst HM, van Kessel B, Bloem AC, van Velzen J, de Jong-Korlaar R, Yuan H, Noort WA, Klein SK, et al. Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab. Leukemia. 2015;29:2039–2049. doi:10.1038/leu.2015.123.
   PubMed Web of Science ®Google Scholar
• Malavasi F. Editorial: CD38 and retinoids: a step toward a cure. J Leukoc Biol. 2011. 90:217–219. doi:10.1189/jlb.0211069.
   PubMed Web of Science ®Google Scholar
• Brennan K, Iversen KF, Blanco-Fernandez A, Lund T, Plesner T, Mc Gee MM. Extracellular vesicles isolated from plasma of multiple myeloma patients treated with daratumumab express CD38, PD-L1, and the complement inhibitory proteins CD55 and CD59. Cells. 2022;11(21):3365. doi:10.3390/cells11213365.
   PubMed Web of Science ®Google Scholar
• Crimeen-Irwin B, Ellis S, Christiansen D, Ludford-Menting MJ, Milland J, Lanteri M, Loveland BE, Gerlier D, Russell SM. Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis. J Biol Chem. 2003. 278:46927–46937. doi:10.1074/jbc.M308261200.
   PubMed Web of Science ®Google Scholar
• Hay J, Carter D, Lieber A, Astier AL. Recombinant Ad35 adenoviral proteins as potent modulators of human T cell activation. Immunology. 2014;144(3):453–460. doi:10.1111/imm.12391.
   PubMed Web of Science ®Google Scholar
• Kassem S, Diallo BK, El-Murr N, Carrie N, Tang A, Fournier A, Bonnevaux H, Nicolazzi C, Cuisinier M, Arnould I, et al. SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Blood. 2022;139(8):1160–1176. doi:10.1182/blood.2021012448.
   PubMed Web of Science ®Google Scholar