CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR) T cell therapy is effective in hematologic cancers but limited in solid tumors.
• Aberrantly glycosylated tumor MUC1 (tMUC1) is present in most breast cancers, including 95% of triple-negative breast cancer (TNBC).
• Monoclonal antibody TAB004 specifically targets tMUC1, sparing normal MUC1.

Purpose of the Study:

• To develop and evaluate MUC28z CAR T cells targeting tMUC1 for TNBC immunotherapy.
• To assess the efficacy and safety of MUC28z CAR T cells in preclinical TNBC models.

Main Methods:

• Human T cells were transduced with MUC28z CAR, comprising TAB004 scFv linked to CD28 and CD3ζ signaling domains.
• MUC28z CAR expression and T cell activation markers were analyzed.
• Target-specific cytotoxicity of MUC28z CAR T cells against TNBC cell lines was assessed.
• Cytokine production (Granzyme B, IFN-γ) was measured upon target cell recognition.
• Efficacy was evaluated in a TNBC xenograft mouse model after a single dose of MUC28z CAR T cells.

Main Results:

• MUC28z CAR was successfully expressed on engineered human T cells.
• MUC28z CAR T cells exhibited significant, target-specific cytotoxicity against TNBC cells.
• Recognition of tMUC1 induced increased production of Th1 cytokines and chemokines.
• A single MUC28z CAR T cell dose markedly inhibited TNBC tumor growth in vivo.
• No significant damage to normal breast epithelial cells was observed.

Conclusions:

• MUC28z CAR T cells demonstrate potent anti-tumor activity against tMUC1-positive TNBC.
• This approach offers a promising therapeutic strategy for TNBC with a favorable safety profile.
• Targeting tMUC1 with CAR T cells represents a viable immunotherapy for breast cancer.