Lymph node models of chronic lymphocytic leukemia for translational evaluation of new drug candidates

INTRODUCTION: In the past decade, targeted agents have revolutionized the treatment landscape for chronic lymphocytic leukemia (CLL) patients, with life expectancy approaching the age-matched population. Despite this , patients can develop drug-associated toxicities or resistance, highlighting a need for further treatment option development. Conventional 2D models often lack the complexity of CLL to appropriately test new agents and promising therapies can lack translatability to patient disease. However, advanced 3D models are emerging that incorporate CLL microenvironment complexity. These human cell-based systems have the potential to replicate patient disease more faithfully and embed physiologically-relevant understanding at an early stage of the drug discovery and development process. AREAS COVERED: Herein, the authors discuss bioengineered human cell-based models that have and are being developed with ranging complexities which can be tuned to fit study requirements, from scaffold-free models (e.g. spheroids), to bioreactors that mimic blood circulation. These platforms offer the potential for both high-throughput drug screening and an enhanced understanding of CLL biology. Literature was retrieved from searches on Google Scholar. EXPERT OPINION: These bioengineered models collectively offer the potential to enhance drug discovery, minimize attrition in the development pathway and bridge the translational gap. This can ultimately facilitate a more efficient translation of effective treatments toward the clinic.