What question did this study set out to answer?

The aim is to develop an IGF-II-based masking domain for the conditional activation of therapeutic antibodies.

May 9, 2026mAbs0 citationsOpen Access

A novel insulin-like growth factor II-based masking domain for conditional activation of therapeutic antibodies

LSLihua Shi MCMinseon Cho MNMotohiko Nishida

Key Points

The aim is to develop an IGF-II-based masking domain for the conditional activation of therapeutic antibodies.
Utilized an infection challenge model with various therapeutic antibodies, including trastuzumab, anti-IL-1β, and bevacizumab.
Engineered IGF-II-s to have no detectable binding to IGF receptors, enhancing masking efficiency.
Assessed protease-dependent activation across multiple antibody types.
IGF-II-s showed stronger masking than native IGF-II, enabling effective conditional activation.
Demonstrated successful protease-dependent activation for trastuzumab, anti-IL-1β, and bevacizumab.
Established the IGF-II-based platform as versatile for improving drug safety and therapeutic windows.

Abstract

infection challenge model at the dose tested. IGF-II-s showed no detectable IGF receptor binding and provided stronger masking than native IGF-II. This generalized approach was demonstrated across multiple antibodies, enabling efficient protease-dependent conditional activation of trastuzumab (anti-HER2), an anti-IL-1β antibody, and bevacizumab (anti-VEGF). Together, these results established an engineered IGF-II-based masking domain as a versatile, IGF-II receptor-silent platform enabling protease-dependent conditional activation of therapeutic antibodies, with potential to improve safety and expand therapeutic windows.

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