Aptamer–biotin–streptavidin–C1q complexes can trigger the classical complement pathway to kill cancer cells.

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Nucleic acid aptamers are emerging as potential therapeutic agents, rivaling antibodies.
• The MUC1 antigen is a target in breast cancer therapy.
• The complement system plays a role in immune responses and cell lysis.

Purpose of the Study:

• To investigate the therapeutic potential of DNA aptamers against MUC1-expressing breast cancer cells.
• To determine if MUC1-specific aptamers can induce complement-mediated cell killing.
• To explore the efficacy and limitations of aptamer-mediated complement activation.

Main Methods:

• Development and application of high-affinity DNA aptamers (MUC1-5TR-1 and MUC1-S1.3/S2.2) against MUC1 antigen.
• Linking aptamers to the first component of complement (C1q) using a biotin–streptavidin system.
• Assessment of MCF7 breast cancer cell viability using Trypan blue uptake and absorbance measurements.

Main Results:

• The aptamer-C1q conjugates demonstrated significant killing of MCF7 cells in vitro.
• The cell killing effect was dose-dependent and reproducible.
• Maximal killing of treated MCF7 cells was approximately 50%, suggesting limitations.

Conclusions:

• MUC1-specific DNA aptamers can be utilized to activate complement and induce cancer cell death.
• Antigen shedding and membrane-bound complement regulatory proteins (mCRPs) may limit the efficacy of aptamer-mediated lysis.
• Future strategies may involve combining anti-MUC1 aptamers with mCRP-specific aptamers for enhanced cancer cell killing, with caution regarding in vivo applications.