Tumor-targeted costimulation by using bi-specific aptamers.

Abstract

Aptamers are chemically synthesized oligonucleotides that can be easily engineered for cancer immunotherapy use. So far, most of the therapeutic aptamers described are antagonistic and block the function of a receptor or its soluble ligand. Recently, aptamers have been modified to act as agonists by multimerization, with a direct application in cancer immunotherapy. Several agonistic aptamers against costimulatory receptors have been described. However, systemic costimulation, though potentially a very potent antitumor immune strategy, is not devoid of auto-inflammatory side effects. In a quest to reduce toxicity and improve efficacy - reducing the therapeutic index - the first bi-specific aptamers to target the costimulatory ligand to the tumor have been described, showing very promising results in different preclinical tumor models.