Frizzled-7-targeting antibody-derived bifunctional protein retargets NK cells against triple-negative breast cancer cells via MICA-NKG2D axis.

ABSTRACT:

Background

Hypoxia is associated with the evasion of triple-negative breast cancer (TNBC) from immune surveillance. Hypoxia increases the subpopulation of putative TNBC stem-like cells (TNBCSCs) through activating Wnt/β-Catenin signaling. The shedding of MHC class I-related chain A (MICA) is particularly noteworthy in cancer stem cells (CSCs), promoting the resistance of CSCs to natural killer (NK) cell cytotoxicity. To reestablish MICA/NKG2D-mediated immunosurveillance, we proposed the design of a fusion protein (SHH002-hu1-MICA) which consists of Frizzled-7 (Fzd7)-targeting antibody and MICA, serving as an engager retargeting NK cells against TNBCs, especially TNBCSCs.

Methods

Opal multicolor immunohistochemistry staining was used to validate the expression of membrane MIC

SUBMITTER: Wang C 

PROVIDER: S-EPMC11873350 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature