Genetically engineering mast cells as effectors for targeted cancer cell cytotoxicity.

Authors

Xiao Han, Di Wen, Ruxing Fu, Jennifer Soto, Yang Song, Yifan Wu, Zejun Wang, Xiao Lin, Jicheng Yu, Tao Sheng, Song Li, Zhen Gu, Kaixin He

Published in

Biomaterials. Volume 338. Issue Pt B. Pages 124699. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

Type-I hypersensitivity is a mast cell-mediated degranulation process induced by IgE-antigen recognition. Inspired by this highly specific mechanism, we developed a new cell therapy platform by genetically engineering mouse mast cell line MC/9 to overexpress the cytotoxic proteins perforin and granzyme B (PG-MCs) via lentiviral transduction. In the melanoma model utilizing B16 cells expressing membrane-bound OVA, a polarized degranulation of mast cells towards cancer cells was validated upon the recognition of antigens by anti-OVA IgE. PG-MCs could selectively kill cancer cells via IgE-antigen recognition. The IgE-sensitized PG-MCs administered through an intertumoral route delivered perforin 1 (Prf1) and granzyme B (Gmzb) toward target cells to potentiate anti-tumor efficacy. Moreover, we demonstrated the reprogramming effect of tumor microenvironment by PG-MC-induced hypersensitivity, driving an immune remodeling of the tumor milieu, characterized by the increased lymphocyte infiltration. In addition, this mast cell therapy, in combination with 5- fluorouracil (5-Fu), induced a significant inhibition of tumor growth in a B16-OVA mouse model, which is associated with the depletion of myeloid-derived suppressor cells (MDSCs).

PMID:
42896419
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

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