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

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-Seida, Takahiro Ishiguro, Takayoshi Tanaka, Takehisa Kitazawa and Mika Endo
Additional contact information
Yuji Sano: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Yumiko Azuma: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Toshiaki Tsunenari: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Yoko Kayukawa: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Junko Shinozuka: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Etsuko Fujii: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Jun Amano: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Yukari Nishito: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Toru Maruyama: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Yasuko Kinoshita: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Yuichiro Sakamoto: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Ayae Yoshida: Chugai Research Institute for Medical Science, Inc., 1-135 Komakado, Gotemba
Yoko Miyazaki: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Yuta Sato: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Chifumi Teramoto-Seida: Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba
Takahiro Ishiguro: Chugai Pharmaceutical Co., Ltd., 1-1Nihonbashi-Muromachi 2-Chome Chuo-ku
Takayoshi Tanaka: Chugai Pharmaceutical Co., Ltd., 1-1Nihonbashi-Muromachi 2-Chome Chuo-ku
Takehisa Kitazawa: Chugai Pharmaceutical Co., Ltd., 200 Kajiwara
Mika Endo: Chugai Pharmaceutical Co., Ltd., 1-1Nihonbashi-Muromachi 2-Chome Chuo-ku

Nature Communications, 2022, vol. 13, issue 1, 1-17

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

Date: 2022
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DOI: 10.1038/s41467-022-32952-3

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