Skip to main content

UNC Breast SPORE Research Project 4

Triple negative breast cancer (TNBC) remains a tumor with poor prognosis even in the era of immune checkpoint inhibitors.

Our focus is on chimeric antigen receptor T cells (CAR-Ts) to target TNBC. We are currently targeting the B7-H3 antigen that is abnormally expressed in several solid tumors, including TNBC, but has limited expression in normal tissues.

We are conducting a Phase I clinical trial to test the safety and antitumor activity of a novel CAR-T therapy in patients with TNBC.

We are also studying new approaches to generating even more effective approaches to T cell-based immunotherapy.

Caption available.
In vivo validation of the antitumor activity of CAR-Ts in the TNBC PDX model in which PDX cells were inoculated in the mammary fat pad and two weeks later mice were infused intravenously with CAR-Ts.

Project Aims

Aim 1

Conduct a Phase I clinical study testing safety and effectiveness of autologous B7-H3.CAR-Ts in patients with TNBC.


Aim 2

Develop preclinical models of TNBC to test dual CAR-Ts targeting B7-H3 and CPSG4 and to engineer dual CAR-Ts to express the CCR2b chemokine receptor, which promotes CAR-T cell trafficking through the blood-brain-barrier when brain metastases produce the CCL2 chemokine.


Aim 3

Assess the mechanism and antitumor activity of Th/Tc17 CAR-Ts activated by cGAMP in modulating the breast cancer tumor microenvironment and enhancing the expansion of CAR-Ts in the tumor microenvironment.


Project Co-Leaders