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.
Highlights
Aptamers are chemically synthesized oligonucleotides that can be engineered for cancer immunotherapy use
The field is leading towards the combination of different immunomodulatory agents that would act in synergism, eliciting a more powerful antitumor immune response [9]
Considering the need to reduce the side effects associated with these cancer immunotherapy strategies, a reasonable approach to improve the therapeutic index would be to deliver the costimulatory artificial ligand only to the tumor, favoring the activation of tumor-reactive lymphocytes and precluding the activation of non-desirable autoreactive immune responses in other parts of the body
Summary
Aptamers are chemically synthesized oligonucleotides that can be engineered for cancer immunotherapy use. Cancer immunotherapy has become a reality upon the recent success of clinical trials in very aggressive tumors with immune-checkpoint blockade antibodies [1, 2]. The antitumor immune response can be tackled by immune-checkpoint blockade, and by favoring T-cell activation, providing artificial costimulatory signals to the tumor-reactive lymphocytes [3].
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