Cancer Nanomedicine: Lessons for Immuno-Oncology

Cancer nanomedicines are currently facing challenges as a result of some recent clinical failures. However, a deeper analysis of the field reveals several nanomedicines that were approved in the past few years. There are several commonalities between the nanomedicines that succeeded in the clinics, including the physicochemical design of the nanomedicines as well as the design of the clinical trials. Cancer nanomedicines preferentially home into tumors, and can result in more than threefold higher drug concentration in the tumor than can be achieved using conventional formulations. There is a trend towards optimizing the design such that more nanomedicines reach the tumor while minimizing systemic loss. A key area of research is to minimize phagocytic uptake by the reticuloendothelial system. With the evolving immunotherapy-based approach to treat cancers, there is an early move in the nanomedicine field to apply the existing nanomedicine knowledge to immunotherapy. It is important to learn from failures in the past as nanotechnology is applied to immunotherapy to prevent repeating the same mistakes. Any studies applying nanotechnology in immuno-oncology need to be mechanistically based and not just observational. Fundamental challenges facing immunotherapy, including early monitoring of efficacy, enabling combinations of immunotherapy and molecularly targeted therapeutics, or converting cold tumors to hot tumors are open topics that can be explored using nanotechnology. The integration of immunotherapy and cancer nanomedicine can emerge as the new paradigm in the treatment of cancer. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades in the search for a cure for cancer. Exciting applications can emerge at the intersection of these two fields. However, it is important to learn from the past successes and failures of cancer nanomedicines for its future applications in cancer immunotherapy. This review discusses the two key parameters that defined clinical success in the case of cancer nanomedicines: (i) physicochemical design principles, and (ii) clinical trial design, which are frequently overlooked in most analyses of the state of the field. Learning from the design principles that defined success for the clinically-used cancer nanomedicines can enable the design of next-generation nanomedicines that can address some of the emerging challenges in cancer immunotherapy, for example (i) enabling combinations of molecularly targeted therapies with immunotherapies that are pharmacologically incompatible; (ii) early monitoring of efficacy of immunotherapies; and (iii) personalizing an immune response to a patient’s tumor. Currently, only a subset of patients treated with immunotherapy exhibit durable response; the integration of nanomedicine and immunotherapy to address the above challenges can lead to new paradigms in the treatment of cancer. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades in the search for a cure for cancer. Exciting applications can emerge at the intersection of these two fields. However, it is important to learn from the past successes and failures of cancer nanomedicines for its future applications in cancer immunotherapy. This review discusses the two key parameters that defined clinical success in the case of cancer nanomedicines: (i) physicochemical design principles, and (ii) clinical trial design, which are frequently overlooked in most analyses of the state of the field. Learning from the design principles that defined success for the clinically-used cancer nanomedicines can enable the design of next-generation nanomedicines that can address some of the emerging challenges in cancer immunotherapy, for example (i) enabling combinations of molecularly targeted therapies with immunotherapies that are pharmacologically incompatible; (ii) early monitoring of efficacy of immunotherapies; and (iii) personalizing an immune response to a patient’s tumor. Currently, only a subset of patients treated with immunotherapy exhibit durable response; the integration of nanomedicine and immunotherapy to address the above challenges can lead to new paradigms in the treatment of cancer.