Combination of T cell-redirecting bispecific antibody ERY974 and chemotherapy reciprocally enhances efficacy against non-inflamed tumours

• DOI: 10.1038/s41467-022-32952-3
• Publication Date: 2022-09-07T13:02:47Z
• Authors: Yuji Sano; Yumiko Azuma; Toshiaki Tsunenari; Yoko Kayukawa; Junko Shinozuka; Etsuko Fujii; Jun Amano; Yukari Nishito; Toru Maruyama; Yasuko Kinoshita; Yuichiro Sakamoto; Ayae Yoshida; Yoko Miyazaki; Yuta Sato; Chifumi Teramoto-...; Takahiro Ishiguro; Takayoshi Tanaka; Takehisa Kitazawa; Mika Endo
• Keywords: Thymidine phosphorylase; Infiltration (HVAC)

Abstract Identifying a strategy with strong efficacy against non-inflamed tumours is vital in cancer immune therapy. ERY974 humanized IgG4 bispecific T cell-redirecting antibody that recognizes glypican-3 and CD3. Here we examine the combination effect of chemotherapy (paclitaxel, cisplatin, capecitabine) treatment xenograft model. monotherapy shows minor antitumour on NCI-H446 xenografted tumours, as infiltration ERY974-redirected cells limited to tumour-stromal boundary. However, therapy improves by promoting cell into tumour centre, increasing distribution tumour. increases capecitabine-induced cytotoxicity capecitabine conversion its active form inducing thymidine phosphorylase expression MKN45 through ERY974-induced IFNγ TNFα cells. We show synergistically reciprocally efficacy, eradicating tumours.