Activity of CAR-T Cell Therapy for Patients with Metastatic Triple Negative Breast Cancer
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.

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.