The anti-DKK1 antibody DKN-01 as an immunomodulatory combination partner for the treatment of cancer

References

• MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26.
   PubMed Web of Science ®Google Scholar
• Goldsberry WN, Londono A, Randall TD, et al. A review of the role of Wnt in cancer immunomodulation. Cancers (Basel). 2019;11:6.
   Google Scholar
• Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003;129(4):199–221.
   PubMed Web of Science ®Google Scholar
• Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–235.
   PubMed Web of Science ®Google Scholar
• Komori Y, Kano J, Nakano N, et al. Dickkopf-related protein 3 promotes cell adhesion and invasion during progression of lung adenocarcinoma. Pathol Int. 2019;69(11):646–654.
   PubMed Web of Science ®Google Scholar
• Glinka A, Wu W, Delius H, et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature. 1998;391(6665):357–362.
   PubMed Web of Science ®Google Scholar
• Chamorro MN, Schwartz DR, Vonica A, et al. FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development. EMBO J. 2005;24(1):73–84.
   PubMed Web of Science ®Google Scholar
• Mao B, Wu W, Li Y, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411(6835):321–325.
   PubMed Web of Science ®Google Scholar
• Niida A, Hiroko T, Kasai M, et al. DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. Oncogene. 2004;23(52):8520–8526.
   PubMed Web of Science ®Google Scholar
• Kagey MH, He X. Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology. Br J Pharmacol. 2017;174(24):4637–4650.
   PubMed Web of Science ®Google Scholar
• Liu Y, Tang W, Xie L, et al. Prognostic significance of dickkopf-1 overexpression in solid tumors: a meta-analysis. Tumour Biol. 2014;35(4):3145–3154.
   PubMedGoogle Scholar
• Lee HS, Lee HE, Park DJ, et al. Clinical significance of serum and tissue Dickkopf-1 levels in patients with gastric cancer. Clin Chim Acta. 2012;413(21–22):1753–1760.
   PubMed Web of Science ®Google Scholar
• Yang H, Chen GD, Fang F, et al. Dickkopf-1: as a diagnostic and prognostic serum marker for early hepatocellular carcinoma. Int J Biol Markers. 2013;28(3):286–297.
   PubMed Web of Science ®Google Scholar
• Jiang T, Huang L, Zhang S. DKK-1 in serum as a clinical and prognostic factor in patients with cervical cancer. Int J Biol Markers. 2013;28(2):221–225.
   PubMed Web of Science ®Google Scholar
• Shizhuo W, Tao J, Shulan Z, et al. The expression and significance of Dickkopf-1 in epithelial ovarian carcinoma. Int J Biol Markers. 2009;24(3):165–170.
   PubMed Web of Science ®Google Scholar
• Malladi S, Macalinao DG, Jin X, et al. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell. 2016;165(1):45–60.
   PubMed Web of Science ®Google Scholar
• D’Amico L, Mahajan S, Capietto AH, et al., Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer. J Exp Med. 2016;213(5): 827–840.
   PubMed Web of Science ®Google Scholar
• Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:3–14.
   PubMed Web of Science ®Google Scholar
• Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
   PubMed Web of Science ®Google Scholar
• Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495–2505.
   PubMed Web of Science ®Google Scholar
• Del Campo JM, Matulonis UA, Malander S, et al. Niraparib maintenance therapy in patients with recurrent ovarian cancer after a partial response to the last platinum-based chemotherapy in the ENGOT-OV16/NOVA trial. J Clin Oncol. 2019;37(32):2968–2973.
   PubMed Web of Science ®Google Scholar
• Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154–2164.
   PubMed Web of Science ®Google Scholar
• Luke JJ, Bao R, Sweis RF, et al. WNT/beta-catenin pathway activation correlates with immune exclusion across human cancers. Clin Cancer Res. 2019;25(10):3074–3083.
   PubMed Web of Science ®Google Scholar
• Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–2520.
   PubMed Web of Science ®Google Scholar
• Chuang J, Chao J, Hendifar A, et al. Checkpoint inhibition in advanced gastroesophageal cancer: clinical trial data, molecular subtyping, predictive biomarkers, and the potential of combination therapies. Transl Gastroenterol Hepatol. 2019;4:63.
   PubMed Web of Science ®Google Scholar
• Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–1235.
   PubMed Web of Science ®Google Scholar
• Abrams T, Hess LM, Zhu YE, et al. Predictors of heterogeneity in the first-line treatment of patients with advanced/metastatic gastric cancer in the U.S. Gastric Cancer. 2018;21(5):738–744.
   PubMed Web of Science ®Google Scholar
• O’Malley DP, Yang Y, Boisot S, et al. Immunohistochemical detection of PD-L1 among diverse human neoplasms in a reference laboratory: observations based upon 62,896 cases. Mod Pathol. 2019;32(7):929–942.
   PubMed Web of Science ®Google Scholar
• Shitara K, Ozguroglu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392(10142):123–133.
   PubMed Web of Science ®Google Scholar
• Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461–2471.
   PubMed Web of Science ®Google Scholar
• Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4(5):e180013.
   PubMed Web of Science ®Google Scholar
• Smyth EC, Moehler M. Late-line treatment in metastatic gastric cancer: today and tomorrow. Ther Adv Med Oncol. 2019;11:1758835919867522.
   Web of Science ®Google Scholar
• Haas MHH, Schurpf-Huber F, Wu Y, et al. Mechanistic insight into anti-tumor activity of DKN-01, a therapeutic antibody with immune modulatory activity [Abstract]. Proceedings of the American association for cancer research annual meeting 2019; 2019 Mar 29–Apr 3; Atlanta (GA), Philadelphia (PA): AACR. Cancer Res 2019; 79(13Suppl):Abstract nr 2404.
   Google Scholar
• Klempner SBJ, Villaflor V, Tenner L, et al. Safety and efficacy of a DKK1 inhibitor (DKN-01) in combination with pembrolizumab (P) in patients (Pts) with advanced gastroesophageal (GE) malignancies. Ann Oncol. 2018;29(Suppl 8):viii222.
   Google Scholar
• Kagey MWY, Zhang X, Sirard C, et al. Therapeutic targeting of the Wnt antagonist DKK1 with a humanized monoclonal antibody in oncology indications [Abstract]. Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1–5; Washington (DC) and Philadelphia (PA): AACR. Cancer Res 2017; 77(13Suppl):Abstract nr 369. doi:10.1158/1538-7445.AM2017-369
   Google Scholar
• Arend RC, Castro C, Matulonis UA, et al. 76 Patients (PTS) with recurrent gynecologic cancer whose tumors have activating wnt pathway mutations respond better to DKN-01, a DICKKOPF-1 (DKK1) inhibitor. Int J Gynecologic Cancer. 2019;29:A40–A41.
   Web of Science ®Google Scholar
• Arend RCCC, Matulonis UA, Hamilton E, et al. Safety and efficacy of a DKK1 inhibitor (DKN-01) as monotherapy or in combination with paclitaxel in patients with Wnt activated recurrent gynecologic malignancies. Gynecol Oncol. 2019;154:34.
   Web of Science ®Google Scholar
• Yang MHM, Heath H, Schurpf-Huber F, et al. Antibody targeting of WNT signaling modulator dickkopf1 (DKK1) enhances innate anti-tumor immunity and complements anti PD-1 and paclitaxel therapy. 33rd annual meeting & pre-conference programs of the society for immunotherapy of cancer (SITC 2018). J Immunother Cancer. 2018;6(1):115.
   PubMedGoogle Scholar
• Edenfield WJRD, Vukelja SJ, Weiss GJ, et al. A phase 1 study evaluating the safety and efficacy of DKN‐01, an investigational monoclonal antibody (Mab) in patients (pts) with advanced non‐small cell lung cancer. J Clin Oncol. 2014;32(5s):8068.
   Google Scholar
• Eads JEKA, Manji G, Abrams T, et al. Phase I study of DKN‐01 (D), an anti‐DKK1 monoclonal antibody, in combination with gemcitabine (G) and cisplatin (C) in patients (pts) with advanced biliary cancer (ABC). Ann Oncol. 2016;27:698P.
   Web of Science ®Google Scholar
• Ryan DPMJ, Mahalingam D, Strickler J, et al. Current results of a phase I study of DKN‐01 in combination with paclitaxel (P) in patients (pts) with advanced DKK1+ esophageal cancer (EC) or gastro‐esophageal junction tumors (GEJ). Ann Oncol. 2016;27:ii108.
   Web of Science ®Google Scholar
• Menezes ME, Devine DJ, Shevde LA, et al. Dickkopf1: a tumor suppressor or metastasis promoter? Int J Cancer. 2012;130(7):1477–1483.
   PubMed Web of Science ®Google Scholar
• Fezza M, Moussa M, Aoun R, et al. DKK1 promotes hepatocellular carcinoma inflammation, migration and invasion: implication of TGF-beta1. PLoS One. 2019;14(9):e0223252.
   PubMed Web of Science ®Google Scholar
• Forget MA, Turcotte S, Beauseigle D, et al. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br J Cancer. 2007;96(4):646–653.
   PubMed Web of Science ®Google Scholar
• Kimura H, Fumoto K, Shojima K, et al. CKAP4 is a Dickkopf1 receptor and is involved in tumor progression. J Clin Invest. 2016;126(7):2689–2705.
   PubMed Web of Science ®Google Scholar
• Kagey MNG, Haas M, Heath H, et al. High tumor expression of DKK1 is associated with improved clinical benefit and longer progression free survival across multiple solid tumors when treated with a target anti-DKK1 antibody (DKN-01). 34th annual meeting & pre-conference programs of the society for immunotherapy of cancer (SITC 2019): part 1. J Immunother Cancer. 2019;7(1):282.
   PubMedGoogle Scholar
• Betella I, Turbitt WJ, Szul T, et al. Wnt signaling modulator DKK1 as an immunotherapeutic target in ovarian cancer. Gynecol Oncol. 2020. DOI:10.1016/j.ygyno.2020.03.010
   PubMed Web of Science ®Google Scholar
• Kaur A, Webster MR, Weeraratna AT. In the Wnt-er of life: Wnt signalling in melanoma and ageing. Br J Cancer. 2016;115(11):1273–1279.
   PubMed Web of Science ®Google Scholar
• Draghiciu O, Lubbers J, Nijman HW, et al. Myeloid derived suppressor cells-an overview of combat strategies to increase immunotherapy efficacy. Oncoimmunology. 2015;4(1):e954829.
   PubMed Web of Science ®Google Scholar