Evaluation of liposomes engineered to bind toll like receptor-2 for complexation of immunostimulatory nucleic acids to target and activate antigen presenting cells

Abstract

Dendritic cells (DCs) have become a major target for tumor therapy. Due to their significant role initiating and coordinating the human immune response, linking the innate and adaptive immune system, DCs seem to be a reasonable starting point for new approaches regarding immune therapy against cancer. Nanocarrier-based delivery systems offer new possibilities in targeting of immune cells by facilitating the uptake of substances and the activation of the respective cells. In this work two different nano carriers (CL419 and CL553) were tested in regard to their ability to target and activate DCs via TLR2 (and TLR7). Furthermore, different viral and synthetical oligonucleotides, serving as adjuvants, were tested, activating DC via TLR9 or STING pathway. Choosing the best performing substances of each group, complexes were formed in order to create a vaccine. The combination of some substances yielded a significant activation of DCs in-vitro. Nevertheless, in-vivo trials have not been performed yet, which will uncover the next hurdles on the path of creating an effective anti-tumor therapy. The application way of the vaccine is to be considered, taking into account the pharmacokinetics and pharmacodynamics, as well as the tumors microenvironment. Concludingly, nano carrier based immune therapy might play an important role in fighting cancer, complementing the common therapies such as chemotherapy, radiation and check point therapy.