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- Title
Combination of T cell-redirecting bispecific antibody ERY974 and chemotherapy reciprocally enhances efficacy against non-inflamed tumours.
- Authors
Sano, Yuji; Azuma, Yumiko; Tsunenari, Toshiaki; Kayukawa, Yoko; Shinozuka, Junko; Fujii, Etsuko; Amano, Jun; Nishito, Yukari; Maruyama, Toru; Kinoshita, Yasuko; Sakamoto, Yuichiro; Yoshida, Ayae; Miyazaki, Yoko; Sato, Yuta; Teramoto-Seida, Chifumi; Ishiguro, Takahiro; Tanaka, Takayoshi; Kitazawa, Takehisa; Endo, Mika
- 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. T-cell redirecting bispecific antibodies have emerged as therapeutic agents to promote T-cell mediated killing of tumor cells. Here the authors show that a combination of chemotherapy and ERY974, a bispecific antibody that targets glypican-3 and CD3, facilitates T cell infiltration and promotes anti-tumor responses also in non-inflamed tumors.
- Subjects
BISPECIFIC antibodies; TUMORS; CANCER chemotherapy; COMBINATION drug therapy; CANCER treatment; THYMIDINE; ANTIBODY-dependent cell cytotoxicity; T cells
- Publication
Nature Communications, 2022, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-32952-3