Forced intracellular degradation of xenoantigens as a modality for cell-based cancer immunotherapy.

Given recent leverage of mesenchymal stromal cells (MSCs) as a potent vaccination platform, we investigated whether forced degradation of an expressed experimental antigen fused to small degron sequences could prime potent antitumoral responses. Retrovirally gene-engineered MSCs were evaluated for their antigen presentation capacity, nature of generated peptide repertoire and therapeutic potency in syngeneic immunocompetent mice with pre-established solid T cell lymphoma. Despite lack of noticeable changes in gene expression, MSC-UBvR-OVA vaccination triggered potent T cell activation which can be attributable to the enriched cell surface presentation of OVA-derived peptides added to elevated mitochondrial reactive oxidative species (ROS) production, the latter being associated with efficient antigen processing.

CD146 Defines a Mesenchymal Stromal Cell Subpopulation with Enhanced Suppressive Properties.

Mesenchymal stromal cells (MSCs) are largely known for their immune-suppressive capacity, hence, their common use in the control of unwanted inflammation. However, novel concepts related to their biology, combined with the urgent need to identify MSC subpopulations with enhanced suppressive properties, drive the search for isolation protocols optimized for clinical applications. We show, in this study, that MSCs expressing high CD146 levels exhibit altered surface expression profiles of CD44 and secrete elevated levels of interleukin (IL)-6, amongst other factors.