Anti-PD-L1 DNA aptamer antagonizes the interaction of PD-1/PD-L1 with antitumor effect

Area of Science:

• Immunology
• Biotechnology
• Oncology

Background:

• Tumor immune evasion, mediated by the PD-1/PD-L1 axis, hinders T cell function and leads to poor patient prognosis.
• This immune suppression pathway is a major mechanism by which cancer cells escape immune surveillance.
• Inhibiting the PD-1/PD-L1 interaction is a key strategy in cancer immunotherapy.

Purpose of the Study:

• To develop a novel aptamer targeting the PD-1/PD-L1 pathway for cancer immunotherapy.
• To evaluate the efficacy of the aptamer in restoring T cell function and inhibiting tumor growth.
• To assess the potential of aptamers as an alternative to traditional antibody therapies.

Main Methods:

• Aptamer selection using cell-SELEX against engineered PD-L1-expressing cells.
• Characterization of aptamer binding affinity (Kd) to PD-L1.
• In vitro assessment of aptamer's ability to restore T cell proliferation and cytokine secretion (IFN-γ).
• In vivo evaluation of aptamer's efficacy in inhibiting CT26 colon carcinoma tumor growth.

Main Results:

• A specific aptamer, PL1, was identified with a binding affinity (Kd) of 95.73 nM to PD-L1.
• Aptamer PL1 successfully inhibited the PD-1/PD-L1 interaction, restoring T cell proliferation and IFN-γ production.
• PL1 demonstrated significant tumor inhibition efficacy against CT26 colon carcinoma in vivo.
• The aptamer exhibited comparable binding and therapeutic effects to antibodies.

Conclusions:

• The aptamer PL1 effectively targets PD-L1, restoring anti-tumor immune responses.
• PL1 shows potential as a therapeutic agent for cancer immunotherapy, offering advantages over antibodies.
• Aptamers represent a promising alternative for cancer treatment due to their specificity, cost-effectiveness, and favorable biophysical properties.