# The emerging role of aptamers in targeted cancer immunotherapy

## TL;DR

Aptamers are emerging as a promising alternative to antibodies in cancer immunotherapy due to their high specificity and modifiability for targeted treatment.

## Contribution

This paper reviews recent advances in aptamer-based cancer immunotherapy, emphasizing their structural evolution and immune checkpoint regulation.

## Key findings

- Aptamers offer advantages over antibodies, including low immunogenicity and ease of synthesis.
- Aptamer-based chimeric systems show potential in T cell activation and tumor-targeted immune modulation.
- Future research should focus on improving in vivo stability and optimizing delivery strategies for clinical use.

## Abstract

Immunotherapy has revolutionized cancer treatment by harnessing the immune system against malignancies; however, traditional antibody-based therapies are hampered by high production costs, immunogenicity, and off-target effects. Aptamers—short, single-stranded DNA or RNA molecules—have emerged as a promising alternative due to their high affinity and specificity, low immunogenicity, ease of chemical synthesis, and versatile structural modifications. These properties position aptamers as powerful tools for targeted drug delivery, immune modulation, and precision cancer therapy. This review highlights recent advances in aptamer-based cancer immunotherapy, focusing on their structural evolution, responsiveness to the tumor microenvironment, and roles in regulating the immune checkpoint. We highlight the development of monospecific, bispecific, and multispecific aptamers, emphasizing their applications in T cell activation, cytokine regulation, and tumor-targeted immune modulation. Additionally, we explore the role of aptamer-based chimeric systems in immunotherapy, including aptamer-small interfering RNA (siRNA) conjugates, aptamer-nanomaterial hybrids, aptamer-drug complexes, and aptamer-exosomes conjugates. Despite progress, challenges remain, such as the need for greater in vivo stability, improved delivery strategies, and optimized multispecific designs. Future research efforts should focus on refining next-generation immune checkpoint-targeting aptamers and expanding their applications in combination immunotherapies. With continued innovation, aptamer-based therapeutics hold the potential to transform cancer immunotherapy, offering safer, more effective, and highly specific treatment options.

Aptamers, with superior specificity and modifiability, overcome antibody limitations in cancer immunotherapy by enabling tumor-responsive targeting and immune checkpoint modulation. The aptamer-based chimeric systems show therapeutic promise, yet require enhanced stability and delivery optimization for clinical translation.