Aptamers Emerge as Programmable Building Blocks for Precision Cancer Immunotherapy

Short single-stranded DNA or RNA molecules known as aptamers are gaining ground as versatile tools for precision cancer immunotherapy, according to a comprehensive review spanning their molecular engineering, pharmacology, and translational potential. The review highlights how aptamer discovery has accelerated through successive generations of selection technology. Conventional SELEX has been joined by Cell-SELEX, in vivo SELEX, high-throughput sequencing, microfluidic selection, and AI-assisted selection, all of which enhance the identification and optimization of aptamers specific to tumor cells and immune cells.

A central challenge for any oligonucleotide drug is survival in the bloodstream, and the review details the chemical modifications developed to address it. PEGylation, 2′-fluoro and 2′-O-methyl substitutions, locked nucleic acids, phosphorothioate linkages, circularization, and lipid or albumin binding have all been deployed to improve nuclease resistance, extend circulation time, and steer biodistribution and tumor accumulation. Functionally, aptamers operate in two modes.

They can directly regulate oncogenic and immune signaling pathways, or serve as targeted delivery vehicles for chemotherapeutic drugs, siRNAs, miRNAs, proteins, peptides, and CRISPR-based systems. Aptamers directed at tumor-associated biomarkers, cancer stem cells, tumor vasculature, stromal components, and immune regulatory pathways could, the authors note, selectively remodel the tumor microenvironment. Combination potential is another strength.

Aptamers are described as well-suited to pairing with immune checkpoint inhibitors, chemotherapy, radiotherapy, photodynamic and photothermal therapy, oncolytic viruses, and cancer vaccines, supporting multifunctional, personalized treatment regimens. Yet the review is candid about remaining hurdles: pharmacokinetics, tumor penetration, off-target effects, manufacturing, long-term safety, regulatory approval, and clinical validation all require further work before aptamer platforms can move from promising pre-clinical results to routine clinical use. Advances in aptamer engineering, nanotechnology, computational design, and biomarker-directed therapy may determine whether these molecules fulfill their potential as next-generation precision cancer immunotherapies.

Subject of Research: Aptamer-based therapeutics for precision cancer immunotherapy

Article Title: Engineering aptamer-based therapeutics for precision cancer immunotherapy: from molecular targeting to clinical applications

Article References: Azhar, M. A., Ahmed, S., Altuhami, A., Shabab, M., Assiri, A. M., Broering, D. C., & Mir, T. A. (2026). Engineering aptamer-based therapeutics for precision cancer immunotherapy: from molecular targeting to clinical applications. Frontiers in Pharmacology, 17, Article 1987479. https://doi.org/10.3389/fphar.2026.1987479

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1987479

Keywords: aptamers, cancer immunotherapy, SELEX, drug delivery, tumor microenvironment, oligonucleotides, chemical modification, targeted therapy, CRISPR, checkpoint inhibitors, nanotechnology, clinical translation