Abstract B034: CpG oligodeoxynucleotides potentiate the antitumor activity of anti-GPC1 antibody

Abstract

Abstract Background: Various monoclonal antibodies targeting tumor antigens have recently been reported. Antitumor monoclonal antibodies greatly depend on antibody-dependent cellular cytotoxicity (ADCC) via tumor-infiltrating natural killer cells and macrophages. We have reported significant antitumor activity of anti Glypican1 (GPC1) monoclonal antibody. The toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotides (ODN) has been widely used as a cancer vaccine adjuvant. Because CpG ODN induce intratumor infiltration of natural killer cells and macrophages, combination therapy with CpG ODN with antitumor monoclonal antibody depending on ADCC may show synergistic antitumor activity. The aim of this study is to evaluate the synergistic antitumor activity of combination therapy with anti GPC1 antibody and CpG ODN. Materials and Method: We examined K3-SPG, which is composed of Schizophyllan (SPG) and K3-CpG ODN. The established human esophageal cancer cell line TE14 was subcutaneously transfected into SCID mice. Xenograft mice were treated by monotherapy with anti GPC1 antibody by intraperitoneal (i.p.) injection and K3-SPG by intratumoral (i.t.) injection twice a week for 4 weeks. Xenograft mice were also treated with combination therapy as follows: (i.p./ i.t.) injection of (A) PBS/ PBS, (B)PBS/ K3-SPG, (C) anti GPC1 antibody/ PBS, (D) anti GPC1 antibody/ K3-SPG, respectively, twice a week for 4 weeks. Antitumor activity was evaluated by measuring the tumor volume twice a week. Tumors were resected 2 weeks after the final treatment and tumor weight was measured. For FACS analysis, agents were administrated twice a week for 2 weeks, and tumors were resected 1 day after the final treatment. Result: Anti GPC1 monoclonal antibody and K3-SPG monotherapy had a significant dose-dependent antitumor activity, respectively. Combination therapy had significant antitumor activity in terms of tumor volumes (A/B/C/D: 605/370/485/247) (mm3) and tumor weight (A/B/C/D: 416/191/317/137) (mg), respectively. FACS analysis revealed that they induced a significant increase in number of macrophage (p=0.02) and high ratio of activated NK cells (p=0.08). Conclusions: Combination therapy with K3-SPG and anti GPC1 monoclonal antibody depending on ADCC may represent a new treatment option for cancer. Citation Format: Yurina Saito, Tsuyoshi Takahashi, Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Kiyokazu Nakajima, Makoto Yamasaki, Ken J. Ishii, Masaki Mori, Yuichiro Doki, Tetsuji Naka. CpG oligodeoxynucleotides potentiate the antitumor activity of anti-GPC1 antibody [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B034.