Bi-specific aptamers mediating tumor cell lysis

Area of Science:

• Biotechnology
• Immunology
• Molecular Biology

Background:

• Antibody-dependent cellular cytotoxicity is crucial for antibody-based tumor therapies.
• This process relies on natural killer cells binding to antibody-coated tumor cells via Fcγ receptor III (CD16).

Purpose of the Study:

• To generate chimeric DNA aptamers that simultaneously target CD16α and c-Met for enhanced tumor cell killing.
• To investigate the efficacy of these bi-specific aptamers in mediating antibody-dependent cellular cytotoxicity.

Main Methods:

• Systematic evolution of ligands by exponential enrichment (SELEX) was used to isolate high-affinity CD16α specific DNA aptamers.
• Two optimized CD16α aptamers were conjugated with c-Met specific aptamers using various linkers to create bi-specific aptamers.
• Binding affinities and simultaneous antigen recognition were assessed.

Main Results:

• Isolated CD16α aptamers demonstrated high specificity and affinity for their targets.
• Bi-specific aptamers maintained binding to both CD16α and c-Met, enabling simultaneous antigen engagement.
• These aptamers effectively mediated cellular cytotoxicity in an aptamer and effector cell concentration-dependent manner.
• Cytotoxicity was reduced when bi-specific aptamers were displaced from CD16α, confirming the mechanism of action.

Conclusions:

• This study presents the first successful linkage of two distinct oligonucleotides into a bi-specific aptamer with a tumor-effective function.
• The developed bi-specific aptamers mediate cellular cytotoxicity, demonstrating a promising new strategy for cancer therapy.