The emerging role of aptamers in targeted cancer immunotherapy

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 <i>in vivo</i> 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.