Funded Grants

Grantee: Weill Cornell Medicine
Project Lead: Claire Vanpouille-Box, PHD
Grant Title: Targeting CAFs to sensitize irradiated glioblastoma to PD-1 blockade 
Program Area: Glioblastoma - Treatment
Grant Type: UKF Seed Grant
Year Awarded: 2021
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma (GBM) is an incurable brain tumor with a median overall survival of 11-15 months. Radiation therapy (RT) is essential for the treatment of brain tumors that is recognized to stimulate immunity in multiple cancers. However, recurrence of brain tumors often occurs in the irradiated brain regions which suggests that RT is not activating the immune system of a patient but is rather participating to brain cancer recurrence. Understanding why this phenomenon is occurring is critical to develop anti-brain cancer strategies that will both exploit the immune activation and the killing of cancer cell to control and cure irradiated brain tumors.

Cancer cell associated fibroblasts (CAFs) emerge as an immune suppressor mechanism generated by RT. Blockade of the fibroblast activation protein alpha (FAP) decreases CAFs and increases T cells into GBM, which suggest that blocking FAP could reactivate immunity against irradiated GBM by removing immunosuppression from CAFs.

In this proposal, we hypothesize that CAFs prevent immune activation and promote survival of irradiated GBM. We will first define and characterize FAP-positive cells in preclinical models of GBM and determine the synergy between FAPi and PD-1 blockade in murine irradiated GBM. If our working model is correct, blocking FAP will restore the immune reactivity of irradiated GBM especially in the context of PD-1 immunotherapy.

Update: This project titled, "Role of FAP-positive cells in immune response to irradiated glioblastoma,” was awarded a R21 research grant funded by the National Cancer Institute (NCI) for 2 years for a total amount of $375,000. 

The R21 project is the sequel of the project that was funded by UKF.

 Award #: 1R21CA280787-01

Aim 1: To determine whether FAP+ cells impair the immunogenicity of irradiated GBM

Aim 2: To determine the synergy between FAP inhibitor and immune checkpoint blockade. 

All preliminary data that was accumulated during the UKF Seed Grant award period was used to submit this proposal for the R21 grant.