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Engineered Fibroblasts as Cell Therapy to Treat Cancer via Tumor Stroma Stabilization
Johns Hopkins University
Gene therapy
Oncology
Hit To Lead or Lead Optimization
• Genetically engineered fibroblasts that are directed to hinder CAF induction into cancer cells to slow cancer recurrence when implanted into cancer-affected tissue.
• It is known cancer cells secrete cytokines inducing normal fibroblasts (NFs) to become carcinoma-associated fibroblasts (CAFs). However, it is not clear how the CAF-promoting cytokines can effectively navigate the dense ECM, a diffusion barrier, in the tumor microenvironment to reach NFs during the early stages of cancer development.
• Inventors have developed genetically engineered fibroblasts, called “Stabilization against Remodeling” (STAR), as a novel advanced cell therapy to be applied following surgery, radiotherapy or chemotherapy.
• Specifically, STAR fibroblasts deliver cross-linking molecules to stabilize extracellular matrix where the primary tumor was to inhibit the diffusion of soluble tumor-promoting factors secreted by residual cancer cells. As demonstrated by in-vitro studies, extracellular matrix stabilization are effective to and prevent carcinoma and stop tumor progression.
WO2021146566A1
Force-dependent extracellular matrix remodeling by early-stage cancer cells alters diffusion and induces carcinoma-associated fibroblasts. Biomaterials, (2020)
