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Updated: Oct 12, 2025
A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
Targeted immunotherapy of triple-negative breast cancer by aptamer-engineered NK cells
Zhenghu Chen1, Zihua Zeng1, Quanyuan Wan1
1Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer comprised of cells that lack expression of targetable biomarkers. Nucleic acid aptamers are a group of molecular ligands that can specifically bind to their targets with high affinity. The ssDNA aptamer PDGC21-T recognizes poorly differentiated cancer cells and tumor tissues through an unidentified cell surface target(s). Because TNBC tumor cells are poorly differentiated, the aptamer PDGC21-T is a promising therapeutic candidate to target TNBC tumor cells. In vitro study revealed that synthetic aptamer probes selectively targeted TNBC cell lines. To assess aptamer immunotherapeutic targeting capability, we generated aptamer-engineered NK cells (ApEn-NK) using aptamer probes as a targeting ligand and NK cells as a therapeutic agent. Cell clustering formation assays revealed that ApEn-NK bound both suspended and adherent TNBC cells with high affinity. In a functional study, ApEn-NK treatment triggered apoptosis and death of cultured TNBC cells. Finally, systemic administration of ApEn-NK in mice harboring TNBC xenografts resulted in significant inhibition of lung metastasis relative to parental NK cell treatments. Unlike chemotherapy, ApEn-NK treatment did not affect body weight in treated mice. We demonstrate a novel approach for targeted TNBC immunotherapy.
Insights
A novel aptamer-engineered NK cell therapy effectively targets triple-negative breast cancer (TNBC) cells. This immunotherapy approach inhibits metastasis and offers a promising treatment option for TNBC without causing weight loss.
Area of Science:
- Biotechnology
- Immunotherapy
- Oncology
Background:
- Triple-negative breast cancer (TNBC) lacks targetable biomarkers, necessitating novel therapeutic strategies.
- Nucleic acid aptamers offer specific molecular targeting capabilities.
- The ssDNA aptamer PDGC21-T shows potential for targeting poorly differentiated cancer cells, including TNBC.
Purpose of the Study:
- To develop and evaluate an aptamer-engineered Natural Killer (NK) cell therapy for triple-negative breast cancer.
- To assess the efficacy of aptamer-engineered NK cells in targeting and eliminating TNBC cells in vitro and in vivo.
Main Methods:
- Generation of aptamer-engineered NK cells (ApEn-NK) utilizing PDGC21-T aptamer probes.
- In vitro assessment of ApEn-NK binding affinity to TNBC cell lines and induction of apoptosis.
- In vivo evaluation of ApEn-NK efficacy in a mouse model of TNBC xenografts, focusing on metastasis inhibition.
Main Results:
- Synthetic aptamer probes selectively targeted TNBC cell lines in vitro.
- ApEn-NK cells demonstrated high-affinity binding to both suspended and adherent TNBC cells.
- ApEn-NK treatment induced apoptosis in cultured TNBC cells and significantly inhibited lung metastasis in vivo.
- ApEn-NK therapy did not cause adverse effects on body weight in treated mice.
Conclusions:
- Aptamer-engineered NK cells represent a novel and effective immunotherapeutic strategy for targeting triple-negative breast cancer.
- This approach shows promise for inhibiting TNBC metastasis with a favorable safety profile compared to chemotherapy.
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