Targeting B7-H3 in Metastatic Renal Cell Carcinoma Using CAR-T Cells
Abstract
Early stage kidney cancer is curable by partial or radical nephrectomy. However, the 5-year survival rate of patients with distant metastasis is less than 20%, without much improvement over the past decade. The adoptive transfer of chimeric antigen receptor (CAR) T cells (CAR-Ts) is emerging as a potential curative approach for cancer patients. Here, I propose that B7-H3 is an ideal candidate for CAR-T-based therapy in renal cell carcinoma (RCC) because it is aberrantly expressed in nearly 20% of tumor cells and 95% of tumor vasculature in clear cell RCC. In my proposal, I will investigate whether CAR-Ts targeting the B7-H3 antigen (B7-H3.CAR-Ts) are effective in RCC and investigate whether B7-H3.CAR-Ts can also target the tumor-associated vasculature. The B7-H3.CAR-Ts I generated are very effective in preclinical models of other B7-H3+ solid tumors such as pancreatic cancer. Thus, I am confident that B7-H3.CAR-Ts can also effectively target B7- H3+ RCC. The project is highly translational, and its long-term goal is to pave the way for developing a clinical trial to treat patients with metastatic RCC using B7-H3.CAR-Ts. If successful, B7-H3.CAR-Ts may represent a curable opportunity for metastatic kidney cancer patients and could also translate to other cancers with B7-H3 expression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810441
Entities
People
- Hongwei Du
Organizations
- United States Army
- University of North Carolina at Chapel Hill