Development of potent Affitin-based bispecific NK cell engagers for the therapy of MSLN-expressing cancers.

ABSTRACT: Well-characterized tumor-associated antigens (TAAs) represent targets of interest in many anticancer therapeutic strategies. Although the use of monoclonal antibodies has led this field for years, the development of smaller molecules, with improved properties, holds great potential for specific anticancer applications. Affitins are small (7 kDa), thermostable, and high-affinity nonimmunoglobulin protein scaffolds derived from archaea. Using ribosome display and next-generation sequencing, we isolated the first Affitins specific for human mesothelin (hMSLN), a TAA overexpressed in many solid cancers and currently targeted in clinical trials. The homodimerization of the most promising Affitin (N13) improved affinity by 60-fold (from 35 nM to 0.57 nM). The high specificity of N13 was demonstr

SUBMITTER: Briolay T 

PROVIDER: S-EPMC12752793 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature