Overcoming biological barriers to improve solid tumor immunotherapy

Cancer immunotherapy has been at the forefront of therapeutic interventions for many different tumor types over the last decade. While the discovery of immunotherapeutics continues to occur at an accelerated rate, their translation is often hindered by a lack of strategies to deliver them specifically into solid tumors. Accordingly, significant scientific efforts have been dedicated to understanding the underlying mechanisms that govern their delivery into tumors and the subsequent immune modulation. In this review, we aim to summarize the efforts focused on overcoming tumor-associated biological barriers and enhancing the potency of immunotherapy. We summarize the current understanding of biological barriers that limit the entry of intravascularly administered immunotherapies into the tumors, in vitro techniques developed to investigate the underlying transport processes, and delivery strategies developed to overcome the barriers. Overall, we aim to provide the reader with a framework that guides the rational development of technologies for improved solid tumor immunotherapy. Graphical abstract