Addressing barriers to effective cancer immunotherapy with nanotechnology: achievements, challenges, and roadmap to the next generation of nanoimmunotherapeutics.

Cancer is a complex systemic disorder that affects many organs and tissues and arises from the altered function of multiple cellular and molecular mechanisms. One of the systems malfunctioning in cancer is the immune system. Restoring and improving the ability of the immune system to effectively recognize and eradicate cancer is the main focus of immunotherapy, a topic which has garnered recent and significant interest. The initial excitement about immunotherapy, however, has been challenged by its limited efficacy in certain patient populations and the development of adverse effects such as therapeutic resistance and autoimmunity. At the same time, a number of advances in the field of nanotechnology have sought to address the challenges faced by modern immunotherapeutics and allow these therapeutic strategies to realize their full potential. This endeavour requires an understanding of not only the immunological barriers in cancer but also the mechanisms by which modern technologies and immunotherapeutics modulate the function of the immune system. Herein, we summarize the major barriers relevant to cancer immunotherapy and review current progress in addressing these obstacles using various approaches and clinically approved therapies. We then discuss the remaining challenges and how they can be addressed by nanotechnology. We lay out translational considerations relevant to the therapies described and propose a framework for the development of next-generation nanotechnology-enabled immunotherapies.