Advances of bifunctional anti-PD-L1/TGF-β fusion protein M7824

Abstract

Hu Mengxue, Xu Bin, Yu Jinming, Song Qibin. Advances of bifunctional anti-PD-L1/TGF-β fusion protein M7824[J]. Journal of International Oncology, 2019, 46(5): 281-284.

［1］ Guo L, Zhang Y, Zhang L, et al. MicroRNAs, TGF-β signaling, and the inflammatory microenvironment in cancer［J］. Tumour Biol, 2016, 37(1): 115-125. DOI: 10.1007/s13277-015-4374-2. ［2］ Akhurst RJ, Hata A. Targeting the TGFβ signalling pathway in disease［J］. Nat Rev Drug Discov, 2012, 11(10): 790-811. DOI: 10.1038/nrd3810. ［3］ Ravi R, Noonan KA, Pham V, et al. Bifunctional immune checkpointtargeted antibodyligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy［J］. Nat Commun, 2018, 9(1): 741. DOI: 10.1038/s41467-017-02696-6. ［4］ Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumourassociated macrophages inhibits phagocytosis and tumour immunity［J］. Nature, 2017, 545(7655): 495-499. DOI: 10.1038/nature22396. ［5］ Moustakas A, Heldin CH. Mechanisms of TGFβ-induced epithelialmesenchymal transition［J］. J Clin Med, 2016, 5(7). pii: E63. DOI: 10.3390/jcm5070063. ［6］ Bai WD, Ye XM, Zhang MY, et al. MiR-200c suppresses TGF-β signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer［J］. Int J Cancer, 2014, 135(6): 1356-1368. DOI: 10.1002/ijc.28782. ［7］ Lin RL, Zhao LJ. Mechanistic basis and clinical relevance of the role of transforming growth factor-β in cancer［J］. Cancer Biol Med, 2015, 12(4): 385-393. DOI: 10.7497/j.issn.20953941.2015.0015. ［8］ Mariathasan S, Turley SJ, Nickles D, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells［J］. Nature, 2018, 554(7693): 544-548. DOI: 10.1038/nature25501. ［9］ Duan J, Liu X, Chen H, et al. Impact of PDL1, transforming growth factorβ expression and tumor-infiltrating CD8⁺T cells on clinical outcome of patients with advanced thymic epithelial tumors［J］. Thorac Cancer, 2018, 9(11): 1341-1353. DOI: 10.1111/1759-7714.12826. ［10］ Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity［J］. Immunol Rev, 2010, 236: 219-242. DOI: 10.1111/j.1600-065x.2010.00923.x. ［11］ Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells［J］. J Exp Med, 2009, 206(13): 3015-3029. DOI: 10.1084/jem.20090847. ［12］ Morikawa M, Derynck R, Miyazono K. TGFβ and the TGFβ family: contextdependent roles in cell and tissue physiology［J］. Cold Spring Harb Perspect Biol, 2016, 8(5). pii: a021873. DOI: 10.1101/cshperspect.a021873. ［13］ Lan Y, Zhang D, Xu C, et al. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β［J］. Sci Transl Med, 2018, 10(424). pii: eaan5488. DOI: 10.1126/scitranslmed.aan5488. ［14］ Knudson KM, Hicks KC, Luo X, et al. M7824, a novel bifunctional antiPD-L1/TGFβ Trap fusion protein, promotes antitumor efficacy as monotherapy and in combination with vaccine［J］. OncoImmunology, 2018, 7(5): e1426519. DOI: 10.1080/2162402X.2018.1426519. ［15］ Jochems C, Tritsch SR, Pellom ST, et al. Analyses of functions of an antiPD-L1/TGFβR2 bispecific fusion protein (M7824)［J］. Oncotarget, 2017, 8(43): 75217-75231. DOI: 10.18632/oncotarget.20680. ［16］ Strauss J, Heery CR, Schlom J, et al. Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors［J］. Clin Cancer Res, 2018, 24(6): 1287-1295. DOI: 10.1158/1078-0432.CCR-17-2653. ［17］ Dovedi SJ, Adlard AL, LipowskaBhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade［J］. Cancer Res, 2014, 74(19): 5458-5468. DOI: 10.1158/0008-5472.CAN-14-1258. ［18］ Grenga I, Donahue RN, Gargulak ML, et al. AntiPDL1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immunemediated recognition and lysis［J］. Urol Oncol, 2018, 36(3): 93. e1-e93. e11. DOI: 10.1016/j.urolonc.2017.09.027. ［19］ David JM, Dominguez C, McCampbell KK, et al. A novel bifunctional antiPD-L1/TGF-β Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells［J］. Oncoimmunology, 2017, 6(10): e1349589. DOI: 10.1080/2162402X.2017.1349589. ［20］ Liu L, Liu X, Ren X, et al. Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification［J］. Sci Rep, 2016, 6: 21602. DOI: 10.1038/srep21602. ［21］ Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as firstline treatment in cisplatinineligible patients with locally advanced and metastatic urothelial carcinoma: a singlearm, multicentre, phase 2 trial［J］. Lancet, 2017, 389(10064): 67-76. DOI: 10.1016/S0140-6736(16)32455-2. ［22］ Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinumtreated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, openlabel, phase 3 randomised controlled trial［J］. Lancet, 2018, 391(10122): 748-757. DOI: 10.1016/S0140-6736(17)33297-X. ［23］ Terabe M, Robertson FC, Clark K, et al. Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy［J］. Oncoimmunology, 2017, 6(5): e1308616. DOI: 10.1080/2162402X.2017.1308616. ［24］ Park BV, Freeman ZT, Ghasemzadeh A, et al. TGF-β1-mediated SMAD3 enhances PD-1 expression on antigen-specific T cells in cancer［J］. Cancer Discov, 2016, 6(12): 1366-1381. DOI: 10.1158/2159-8290.CD-15-1347. ［25］ Luis G, Tae K, David VB, et al. Results from a secondline (2L) NSCLC cohort treated with M7824 (MSB0011359C), a bifunctiona fusion protein targeting TGF-β and PD-L1［J］. J Clin Oncol, 2018, 36 (15_Suppl): 9017. DOI: 10.1200/JCO.2018.36.15_suppl.9017. ［26］ Julius S, Margaret GM, Jason R, et al. Safety and activity of M7824, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with HPV associated cancers［J］. J Clin Oncol, 2018, 36 (15_Suppl): 3007. DOI: 10.1200/JCO.2018.36.15_suppl.3007. ［27］ Yoo C, oh DY, Choi HJ, et al. AB053. P-21. M7824 (MSB0011359C), a bifunctional fusion protein targeting transforming growth factor β (TGF-β) and PD-L1, in Asian patients with pretreated biliary tract cancer (BTC): efficacy by BTC subtype［J］. ESMO, 2019, In press. DOI: 10.21037/hbsn.2019.AB053.

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Advances of bifunctional anti-PD-L1/TGF-β fusion protein M7824

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