Organ-on-a-chip models for development of cancer immunotherapies

Abstract

Cancer immunotherapy has emerged as a promising approach in the treatment of diverse cancer types. However, the development of novel immunotherapeutic agents faces persistent challenges due to poor translation from preclinical to clinical stages. To address these challenges, the integration of microfluidic models in research efforts has recently gained traction, bridging the gap between in vitro and in vivo systems. This approach enables modeling of the complex human tumor microenvironment and interrogation of cancer-immune interactions. In this review, we analyze the current and potential applications of microfluidic tumor models in cancer immunotherapy development. We will first highlight current trends in the immunooncology landscape. Subsequently, we will discuss recent examples of microfluidic models applied to investigate mechanisms of immune-cancer interactions and for developing and screening cancer immunotherapies in vitro. First steps toward their validation for predicting human in vivo outcomes are discussed. Finally, promising opportunities that microfluidic tumor models offer are highlighted considering their advantages and current limitations, and we suggest possible next steps toward their implementation and integration into the immunooncology drug development process.