Towards synthetic immune cells for cancer immunotherapy
Most cellular therapies targeting cancer require culture of autologous cells. The dedicated facilities and personnel needed, the variability in quality of the product depending on the condition of the patient and state of disease, hamper widespread use. In an attempt to generate an of the shelf product to target cancer we exploited the ever expanding possibilities to build supramolecular structures offered by chemistry to mimic nature including the construction of artificial immune cells or functions thereof. Effective immunotherapy critically depends on efficient production of antigen specific cytotoxic T cells. Herein lies an opportunity for both chemists and immunologists to design and synthesize so called artificial antigen presenting cells (aAPCs) that can generate in vivo T cell expansion. We have designed a novel synthetic dendritic cell (sDC) that possesses essential features of natural DCs. Our sDC is based on a semi flexible poly(isocyano peptide) polymer and, as proof of principle, carries both anti CD3 antibodies for triggering the T cell receptor/CD3 complex as well as anti CD28 antibodies as a co stimulatory signal. Multiple copies of both antibodies facilitate multivalent binding similar to natural DCs. The high mobility of these polymer bound antibodies, reminiscent of protein motility in a natural plasma membrane, enables receptor rearrangements to occur during T cell activation. We observed effective T cell activation at significantly lower antibody concentrations than freely soluble antibodies. We also demonstrate antigen specific T cell activation when MHC/peptide complexes were bound. These findings demonstrate the potential of multifunctional polymers for mimicking functions of natural DCs or other immune cells, paving the way for their exploitation in immunotherapeutic strategies. Citation Format: Carl G. Figdor, Subhra Mandal, Roel Hammink, Loek Eggermont, Jorieke Weiden, Dion Voerman, Jurjen Tel, Zaskia H. Eksteen Akeroyd, Kerstin Blank, Alan E. Rowan. Towards synthetic immune cells for cancer immunotherapy. [abstract] In: Proceedings of the CRI CIMT EATI AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16 19, 2015; New York, NY. Philadelphia (PA) AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA29.