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Selection of PD1/PD-L1 X-Aptamers
Hongyu Wang1, Curtis H Lam2, Xin Li1
1Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, TX, 77030, USA.
Biochimie
|September 16, 2017
Summary
Chemically modified aptamers (X-Aptamers) were developed to target immune checkpoint proteins Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1). These novel aptamers show potential for mimicking antibody functions in vitro.
Area of Science:
- Biotechnology
- Molecular Biology
- Immunology
Background:
- Immune checkpoint proteins, such as PD-1 and PD-L1, are critical regulators of the immune response.
- Dysregulation of the PD-1/PD-L1 pathway is implicated in various cancers, making them significant therapeutic targets.
- Antibodies are currently the primary therapeutic agents targeting this pathway, but aptamers offer potential advantages.
Purpose of the Study:
- To identify and characterize novel chemically modified aptamers (X-Aptamers) targeting human Programmed Death 1 (hPD-1) and Programmed Death Ligand 1 (hPD-L1).
- To evaluate the binding affinity, specificity, and functional mimicry of antibody-like functions of the selected aptamers.
- To explore the potential of these aptamers as diagnostic or therapeutic agents against cancer.
Main Methods:
- Selection of aptamers using a bead-based X-Aptamer (XA) library with chemically modified nucleotides.
- Characterization of aptamer binding to recombinant PD-1 and PD-L1 proteins.
- Validation of aptamer binding specificity using cells expressing hPD-1 and hPD-L1.
- Assessment of aptamer binding to human pancreatic ductal adenocarcinoma tissue.
- In vitro assays to evaluate the functional mimicry of antibody functions by the aptamers.
Main Results:
- Specific X-Aptamers targeting PD-1 (XA-PD1) and PD-L1 (XA-PDL1) were successfully identified.
- The selected aptamers demonstrated high binding affinity and specificity for their respective targets.
- Validation confirmed binding to target proteins on cell surfaces and in human tumor tissue.
- In vitro functional assays indicated that the aptamers could mimic antibody functions.
Conclusions:
- Chemically modified aptamers (X-Aptamers) represent a promising new class of molecules for targeting immune checkpoints PD-1 and PD-L1.
- These aptamers exhibit specific binding and functional characteristics comparable to antibodies.
- Further development of these aptamers could lead to novel diagnostic and therapeutic strategies in cancer immunotherapy.
