Magnetic Nanostructures as Emerging Therapeutic Tools to Boost Anti-Tumour Immunity

SIMPLE SUMMARY: Immunotherapy represents an attractive therapeutic option for effective treatment of different forms of cancers. However, many patients exhibit primary or acquired resistance to conventional immunotherapies. In recent years, the encapsulation of immunotherapeutics into nanoparticles is emerging as a promising strategy to improve the responsiveness of immunologically “cold” tumors. Among the several types of nanoparticles explored for cancer immunotherapy, magnetic nanoparticles are particularly interesting since they act as carriers for immunotherapeutic agents and display self-adjuvanting properties. In addition, the ability of magnetic nanostructures to respond to an altering magnetic field (AMF) can be exploited to facilitate the movement of therapeutic-loaded nanoparticles at the desired site or promote localized heating for the thermal ablation of tumors. This review examines the peculiar properties of magnetic nanoparticles and how they can be harnessed for the design of innovative single or combinatorial cancer immunotherapies. ABSTRACT: Cancer immunotherapy has shown remarkable results in various cancer types through a range of immunotherapeutic approaches, including chimeric antigen receptor-T cell (CAR-T) therapy, immune checkpoint blockade (ICB), and therapeutic vaccines. Despite the enormous potential of cancer immunotherapy, its application in various clinical settings has been limited by immune evasion and immune suppressive mechanisms occurring locally or systemically, low durable response rates, and severe side effects. In the last decades, the rapid advancement of nanotechnology has been aiming at the development of novel synthetic nanocarriers enabling precise and enhanced delivery of immunotherapeutics, while improving drug stability and effectiveness. Magnetic nanostructured formulations are particularly intriguing because of their easy surface functionalization, low cost, and robust manufacturing procedures, together with their suitability for the implementation of magnetically-guided and heat-based therapeutic strategies. Here, we summarize and discuss the unique features of magnetic-based nanostructures, which can be opportunely designed to potentiate classic immunotherapies, such as therapeutic vaccines, ICB, adoptive cell therapy (ACT), and in situ vaccination. Finally, we focus on how multifunctional magnetic delivery systems can facilitate the anti-tumour therapies relying on multiple immunotherapies and/or other therapeutic modalities. Combinatorial magnetic-based therapies are indeed offering the possibility to overcome current challenges in cancer immunotherapy.