U3-1402, a novel HER3-targeting antibody-drug conjugate, for the treatment of Colorectal Cancer

Molecular Cancer Therapeutics
Shigehiro KoganemaruToshihiko Doi

Abstract

HER3 (human epidermal growth factor receptor 3) is overexpressed in several cancers including colorectal cancer (CRC). Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC), composed of the HER3 antibody patritumab and a novel topoisomerase I inhibitor, DX-8951 derivative (DXd). The sensitivity of DXd was evaluated by a growth inhibition assay. The antitumor activity of U3-1402 was evaluated in a murine xenograft model in which its effects on cells, with a range of HER3 expression levels, were compared with those of patritumab alone, irinotecan, control-ADC and saline. In the growth inhibition assay, all CRC cell lines were sensitive to DXd. In the tumor xenograft model, significant tumor regression with U3-1402 was observed both in the DiFi cell line (high HER3 expression; KRAS wild type) and in SW620 (high HER3 expression; KRAS mutation), but no treatment effect was observed in Colo320DM (low HER3 expression). Notably, SW620 tumor growth was significantly suppressed with U3-1402 compared with the saline-treated group (P < 0.001) and showed greater activity compared with the irinotecan group. By contrast, ...Continue Reading

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Apr 25, 2020·EMBO Molecular Medicine·Lucía Gandullo-SánchezAtanasio Pandiella
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Jul 8, 2021·Scientific Reports·Nadine AschmoneitRoland E Kontermann

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