Genetic engineering of FGFR2+ fibrocytes as vehicles for IL12 targeting Esophageal Squamous Cell Carcinoma
Grant Data
Project Title
Genetic engineering of FGFR2+ fibrocytes as vehicles for IL12 targeting Esophageal Squamous Cell Carcinoma
Principal Investigator
Professor Guan, Xin-Yuan
(Project Coordinator (PC))
Co-Investigator(s)
Ms Huang Jiao
(Co-Investigator)
Mr Lam Kwong Yiu
(Co-Investigator)
Duration
12
Start Date
2022-04-01
Completion Date
2023-03-31
Amount
264600
Conference Title
Genetic engineering of FGFR2+ fibrocytes as vehicles for IL12 targeting Esophageal Squamous Cell Carcinoma
Keywords
Esophageal Squamous Cell Carcinoma, FGFR2+ fibrocytes, Genetic engineering, IL12
Discipline
Others - Medicine, Dentistry and Health
HKU Project Code
InP/029/22
Grant Type
Researcher Programme (Innovation and Technology Fund) (RP-ITF)
Funding Year
2021
Status
Completed
Objectives
Esophageal carcinoma ranks as the 6th most common cancer and in Hong Kong, most of patients are diagnosed as esophageal squamous cell carcinoma (ESCC). Since the cancer-homing ability of FGFR2(+) fibrocytes and the hypoxic tumor microenvironment, we aim to develop a novel therapy by transferring proinflammatory IL12 cytokine to stimulate anti-tumor immunities. R&D methodology: FGFR2(+) fibrocytes are isolated from human peripheral blood mononuclear cells and then transfected with a hypoxia responsive element (HRE) induced IL12 gene, a proinflammatory cytokine promoting anti-tumor immunities. After ex vivo expansion of FGFR2(+) fibrocytes using cytokines such as IL-1, the engineered cells will be injected into mice to observe the anti-tumor effect. Meanwhile, the distribution of FGFR2(+) fibrocytes in organs, plasma concentration of IL12 and corresponding side effects will be monitored. Impact and benefits: Given the tumor trophism of FGFR2(+) fibrocytes, the genetic engineered cells have the ability to carry an anti-tumor inducing factor, IL12, and lead to anti-tumor immunity. This novel therapy could provide a more powerful and precise treatment targeting cancer and avoid off-target cytotoxicities. In addition to this, IL12 transfected FGFR(+) fibrocytes could also maintain a continuous IL12 delivery in tumor microenvironment to enhance anti-tumor effects.