Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer

Area of Science:

• Oncology
• Immunotherapy
• Cancer Biology

Background:

• Triple-negative breast cancer (TNBC) lacks effective therapies due to the absence of specific surface targets.
• Tissue factor (TF) is identified as a viable target in a significant proportion of TNBC cases.
• Existing treatments for TNBC remain limited, highlighting an unmet clinical need.

Purpose of the Study:

• To develop and evaluate TF-targeting CAR-NK cells for TNBC immunotherapy.
• To assess the efficacy of TF-CAR-NK cells as a single agent and in combination with L-ICON.
• To establish the potential of TF as a target for CAR-NK cell-based cancer treatment.

Main Methods:

• Development of TF-targeting CAR-engineered natural killer (TF-CAR-NK) cells.
• Preclinical in vitro assessment of TF-CAR-NK cell cytotoxicity against TNBC cells.
• In vivo evaluation of TF-CAR-NK cell efficacy in TNBC xenograft mouse models.
• Combination therapy assessment with L-ICON, a TF-targeting immunoconjugate, utilizing ADCC.

Main Results:

• TF-CAR-NK cells demonstrated significant killing of TNBC cells in vitro.
• The combination of TF-CAR-NK cells and L-ICON enhanced anti-tumor activity via ADCC.
• TF-CAR-NK cells exhibited potent anti-tumor efficacy in both cell line- and patient-derived xenograft models.
• The study confirmed TF as a targetable surface antigen for CAR-NK immunotherapy in TNBC.

Conclusions:

• TF-CAR-NK cells represent a promising novel immunotherapy for TNBC.
• Targeting TF with CAR-NK cells, especially in combination with L-ICON, offers a potential new therapeutic avenue.
• This research provides a proof of concept for TF-targeted CAR-NK immunotherapy in TNBC, warranting further investigation.