Genetic engineering of FGFR2+ fibrocytes as vehicles for IL12 targeting Esophageal Squamous Cell Carcinoma

Professor Guan, Xin-Yuan   (Project Coordinator (PC))

Ms Huang Jiao   (Co-Investigator)

Mr Lam Kwong Yiu   (Co-Investigator)

12

2022-04-01

2023-03-31

264600

Genetic engineering of FGFR2+ fibrocytes as vehicles for IL12 targeting Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma, FGFR2+ fibrocytes, Genetic engineering, IL12

Others - Medicine, Dentistry and Health

InP/029/22

Researcher Programme (Innovation and Technology Fund) (RP-ITF)

2021

Completed

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.