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Updated: Jul 26, 2026
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer
Martin J Raftery1, Alexander Sebastian Franzén1, Clarissa Radecke2
1Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Abstract:
There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified CD44v6, an adhesion molecule expressed in lymphomas, leukemias and solid tumors that is implicated in tumorigenesis and metastases. We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. We could show that CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models. The IL-15 superagonist was specifically released upon recognition of CD44v6 on TNBC and contributed to the cytotoxic attack. PD1 ligands are upregulated in TNBC and contribute to the immunosuppressive tumor microenvironment (TME). Competitive inhibition of PD1 neutralized inhibition by PD1 ligands expressed on TNBC. In total, CD44v6 CAR-NK cells are resistant to TME immunosuppression and offer a new therapeutic option for the treatment of BC, including TNBC.
Insights
New chimeric antigen receptor (CAR) natural killer (NK) cells targeting CD44v6 show promise for treating triple-negative breast cancer (TNBC). These engineered NK cells overcome tumor immunosuppression, offering a potential new therapy for this challenging cancer.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) lacks effective targeted therapies.
- Chimeric antigen receptor (CAR) natural killer (NK) cells are an emerging cancer treatment modality.
- CD44v6 is identified as a potential therapeutic target in TNBC.
Purpose of the Study:
- To develop and evaluate a novel CAR-NK cell therapy targeting CD44v6 for TNBC.
- To engineer CAR-NK cells with enhanced anti-tumor activity and resistance to the tumor microenvironment (TME).
Main Methods:
- Development of a next-generation CAR targeting CD44v6, incorporating IL-15 superagonist and checkpoint inhibitor functionalities.
- Assessment of CD44v6 CAR-NK cell cytotoxicity against TNBC using 3D spheroid models.
- Evaluation of the role of IL-15 superagonist release and PD-1/PD-1 ligand interaction in therapeutic efficacy.
Main Results:
- CD44v6 CAR-NK cells exhibited potent cytotoxicity against TNBC in 3D models.
- IL-15 superagonist release was triggered by CD44v6 recognition, enhancing cytotoxic attack.
- Engineered CAR-NK cells demonstrated resistance to PD-1 ligand-mediated immunosuppression within the TME.
Conclusions:
- CD44v6 CAR-NK cells represent a promising therapeutic strategy for TNBC.
- This approach overcomes TME-induced immunosuppression, offering a novel treatment option for breast cancer (BC).
