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<p>Antibody conjugates play a central role across multiple healthcare sectors with a prime example being antibody-drug conjugates (ADCs). Although widely used lysine and hinge cysteine conjugation methods yield products, the lack of site-specificity and spatial control along with the highly heterogeneous composition are significant limitations. Herein, we describe a facile supramolecular assembly method based on heterodimer coiled-coil formation for site-specific antibody conjugation that perseveres antibody antigen binding sites for target engagement. The platform method affords uniform loading of diverse payloads including anti-cancer agents, polymers, enzymes, fluorophores, etc. under mild aqueous conditions. Further, the facile convergent approach capitalizes on the independent strengths and flexibility of protein expression and peptide chemistry culminating in a final self-assembly step. An ADC loaded with monomethyl auristatin E targeting ErbB2/Her2 positive tumors significantly reduces tumor volume in a human ovarian cancer xenograft model outperforming the antibody alone with validated performance against a best-in-class therapeutic.</p>

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Supramolecular coiled-coil peptide platform for site-specific antibody drug conjugate engineering

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月2日

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  • Alina Ringaci,
  • Ting-Yu Shih,
  • Mark W. Grinstaff

摘要

Antibody conjugates play a central role across multiple healthcare sectors with a prime example being antibody-drug conjugates (ADCs). Although widely used lysine and hinge cysteine conjugation methods yield products, the lack of site-specificity and spatial control along with the highly heterogeneous composition are significant limitations. Herein, we describe a facile supramolecular assembly method based on heterodimer coiled-coil formation for site-specific antibody conjugation that perseveres antibody antigen binding sites for target engagement. The platform method affords uniform loading of diverse payloads including anti-cancer agents, polymers, enzymes, fluorophores, etc. under mild aqueous conditions. Further, the facile convergent approach capitalizes on the independent strengths and flexibility of protein expression and peptide chemistry culminating in a final self-assembly step. An ADC loaded with monomethyl auristatin E targeting ErbB2/Her2 positive tumors significantly reduces tumor volume in a human ovarian cancer xenograft model outperforming the antibody alone with validated performance against a best-in-class therapeutic.