CellularNanoMachines · Development of Stimuli-Responsive Nanoparticle-carrying T lymphocytes in the Fight against Cancer

Development of Stimuli-Responsive Nanoparticle-carrying T lymphocytes in the Fight against Cancer

Cancer immunotherapy has been recently erected as the fourth pillar of treatment modalities, along with radiotherapy, surgery, and chemotherapy. Since 2010, numerous clinical trials infusing ex vivo expanded tumor-specific T lymphocytes have demonstrated tumor regression in patients with blood-related tumors. Unfortunately, treatment of solid tumors with similar approaches has yielded less favorable results. Poor trafficking of T cells to the tumor tissue as well as their low ability to survive and/or expand in the hostile tumor microenvironment are two of the main limitations raised in initial clinical trials. Therefore, new strategies able to control and modulate the lifespan and function of antitumor immune cells in solid tumors are urgently needed. Here, we aimed to find innovative ways to make smart cell-based machines, that is, hybrid systems capable of producing synergistic effects between nanoparticles (NPs) and immune cells towards aforementioned clinical needs. The design would consist of human T cells containing magnetic NPs (coined “magnetic cells”). The tumor-homing “magnetic cells” (guided by an external magnetic field) would facilitate T cell infiltration into tumors to improve T cell infiltration in tumors and potentially enhance the performance of cell therapies. More specifically, the research objectives for this project can be listed as follows: (1) to design, synthesize and characterize independent NPs based on iron oxide materials; (2) to synthesize and characterize polymers containing “clickable” groups for cell surface-grafting and NP-anchoring; (3) to internalize the different NPs into T cells using innovative bioconjugate chemistry, and; (4) to evaluate and validate—iterative loop—the accumulation of these NP-cell hybrid systems into tumors using PET, and/or optical imaging techniques. After the completion of this project, a family of water-soluble zinc-doped iron oxide NPs have been prepared. These NPs have been fully-characterized (TEM, DLS, z-potential, magnetism) and demonstrated optimal biocompatible properties as well as excellent magnetic performance. In vitro studies (using confocal microscopy and flow cytometry) also demonstrated that these NPs can interact with T cells of different origin, and that, the resulting hybrid “NP-cell” adducts can be efficiently magnetized and moved towards a NdFeB magnet. Using optical and nuclear in vivo imaging techniques, we demonstrated that these “magnetic cells” could circulate to tumors more efficiently than control T cells (without NPs). This improved targeting behavior could be attributed to the influence that an external magnetic field exerts on the magnetic NPs, attracting the hybrid systems (NP-T cells) to the targeted area.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз