Aptamer based cancer immunotherapy

A promising strategy in cancer immunotherapy is the employment of a bispecific agent that can bind with both tumour markers and immunocytes for recruitment of lymphocytes to tumour sites and enhancement of anticancer immune reactions. Until recently, chimeric antigen receptor T (CAR-T) cell therapy and immune checkpoint blockade (ICB) are the remarkable therapies observed. However, CAR-T therapy is extremely expensive due to the cost of T-cells culturing, processing, storage, and transportation. ICB, such as PD-1/PD-L1 antibodies, can stimulate patient’s immune system resulting in anti-tumour immune activities including autoimmune effects that have caused lethal outcomes. Aptamers have emerged as a new therapeutic class of reagents highly suitable for cancer immunotherapy.

Platforms incorporating aptamers can be used to tackle the three major challenges in cancer immunotherapy including:

  • Blockade of immunosuppressive mechanisms
  • Activation of the agonistic immune receptors
  • Increase of the tumour immunogenicity

Taking advantage of the high specificity and affinity of aptamers, Li et al., 2019 constructed the first bivalent, bispecific aptamer (BBiApt) targeting both MUC1 positive tumour cells and CD16-positive lymphocytes. This aptamer consisted of two MUC1 aptamers and two CD16 aptamers linked together by three 60 nt DNA spacers (Figure 1). The goal of the BBiApt was to engage CD16-positive immunocytes with MUC1 – positive cancer cells in order to selectively enhance the antitumour cytotoxicity.

Figure 1. Design of bivalent, bispecific aptamer (BBiApt): A – Scheme of BBiApt recruiting CD16 – positive immunocytes to MUC1-positive tumour cells B- The predicted secondary structure of BBiApt.

Results showed that together BBiApt and CD16 aptamer showed strong binding to the target cells as compared to the negative cells (Figure 2). High affinity was generated by bivalent aptamer BBiApt to the target cells as compared with monovalent MUC1 or CD16 aptamers. Moreover, BBiApt successfully recruited lymphocytes to cancer cells and facilitated immune cytotoxicity in vitro.

Figure 2. Binding of BBiApt and monovalent MUC1 or CD16 aptamers to target (MUC1 positive) and control (MUC1 negative) cells. BBiApt showed higher binding to target cells (A and B) as compared to control cells (C and D) by flow cytometry. Immune cytotoxicity of BBiApt to target (E) and control (F) cells analysed by MTS assay.

Overall the results indicated that aptamer – based multivalent bispecific agents may potentially serve as a new approach to selectively boost anti-tumour immune reactions. At Aptamer Group Limited (AGL), we offer the advantage of designing aptamers to be optimized for the conditions you want to use them in. This way they are engineered to bind to their target with high specificity and affinity. Moreover, AGL continuously aims to conduct further research in prevention, diagnosis and treatment of cancer. If you would like to know more about aptamers and their applications in diagnostics and therapeutics, please contact us using the form below.

Reference:

Li Z, Hu Y, An Y, Duan J, Li X, Yang XD (2019). Novel bispecific aptamer enhances immune cytotoxicity against MUC1-Positive tumor cells by MUC1-CD16 dual targeting. Molecules. 24(3): 478. doi:10.3390/molecules24030478

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