What question did this study set out to answer?

To assess the efficacy of SCR-A019, a biparatopic ADC targeting mesothelin, and its potential in overcoming MSLN shedding issues.

April 5, 2026

Abstract 3185: SCR-A019, a first-in-class biparatopic ADC targeting MSLN, with a novel topoisomerase I inhibitor demonstrates encouraging efficacy in preclinical models

Key Points

To assess the efficacy of SCR-A019, a biparatopic ADC targeting mesothelin, and its potential in overcoming MSLN shedding issues.
Developed SCR-A019, a biparatopic ADC linked to a topoisomerase I inhibitor.
Conducted in vitro cytotoxicity assays comparing SCR-A019 to benchmark ADCs.
Evaluated anti-tumor efficacy in multiple tumor cell lines and MSLN-positive tumor xenografts in vivo.
SCR-A019 demonstrated enhanced binding and internalization compared to traditional monoclonal ADCs.
It induced significant tumor cell lysis in the presence of soluble mesothelin.
In vivo studies showed dose-dependent anti-tumor activity against lung and ovarian cancer xenografts, outperforming benchmark ADCs.

Abstract

Abstract Background: Mesothelin (MSLN) is a GPI-anchored glycoprotein that is expressed on many cancers but limited in normal tissues, which makes it an attractive target for antibody-based cancer therapy. However, MSLN is shed from surface of cells at high levels via proteases that cleave at its membrane-proximal C-terminal region. Shed MSLN accumulates in patient fluids and tumors and can block anti-MSLN antibodies from killing cancer cells. To overcome the challenge of MSLN shedding, we developed a novel biparatopic ADC which prefers binding to membrane MSLN rather than soluble MSLN. Method Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3185.

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Cite This Study

Wang et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd9ca79560c99a0a3b27 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-3185

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