Aptamers: A New Technological Platform in Cancer Immunotherapy

Abstract

The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far, monoclonal antibodies may currently be the most successful immuno-tools used to that end. The number of ongoing clinical trials with monoclonal antibodies has been increasing exponentially over the last few years upon the Food and Drug Administration (FDA) approval of the first immune-checkpoint blockade antibodies. In spite of the proved antitumor effect of these reagents, the unleashing of the immune system to fight cancer cells has a cost, namely auto-inflammatory toxicity. Additionally, only a small fraction of all patients treated with immune-checkpoint antibodies have a clinical benefit. Taking into account all this, it is urgent new therapeutic reagents are developed with a contained toxicity that could facilitate the combination of different immune-modulating pathways to broaden the antitumor effect in most cancer patients. Based on preclinical data, oligonucleotide aptamers could fulfill this need. Aptamers have not only been successfully used as antagonists of immune-checkpoint receptors, but also as agonists of immunostimulatory receptors in cancer immunotherapy. The simplicity of aptamers to be engineered for the specific delivery of different types of cargos to tumor cells and immune cells so as to harvest an efficient antitumor immune response gives aptamers a significant advantage over antibodies. In this review all of the recent applications of aptamers in cancer immunotherapy will be described.

A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

“… 13 , 18 , 19 , 20 Recent aptamer-related research has further extended the field into functional aptamer therapeutics, especially in the field of immuno-oncology, an area full of new hope and uncertainty. 10 , 21 Because the immune checkpoint landscape encompasses multiple positive and negative regulators, aptamers may have several advantages over mAbs in cancer immunotherapy per se. For example, it is possible to engineer aptamers with dual desirable functions, either being a dual antagonist or an agonist-antagonist integrative.…”

Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy

“…Up to the present time, a number of aptamers have been developed that are capable of modulating immune responses against cancer cells. These aptamers were used either as antagonists of immune checkpoints or as agonists of immuno-stimulatory receptors [147].…”

Application and development of aptamer in cancer: from clinical diagnosis to cancer therapy

“…For instance, The anticancer aptamers chimera systems are able to specifically bind to tumor cells and deliver their drugs to the target cells 69 . Aptamers chimera systems also can be designed with the capability of concurrent binding to cancer cells and lymphocytes, which can induce an enhanced antitumor and cellular immunity by simultaneous targeting of cancer cells and the immune cells 70 .…”