Cellular immunoTHERapy modelling by exploitation of humanized OSSicles

Bones represent a privileged site for cancer initiation and metastasis. Yet, current in vitro and animal models fall short in accurately recapitulating bone-developing cancers. To address this, we developed the human ossicle (hOss) technology: the in vivo formation of miniaturized bone organs composed of patient-derived bone and marrow cells. By mimicking the patient’s bone microenvironment, hOss offer a personalized model for studying bone-related cancers. To ensure reproducibility and standardization, we further developed OssiGel—a customized extracellular matrix that reliably supports robust hOss formation from patient-derived cells. This innovation paves the way for advanced therapy testing, particularly for cellular immunotherapies, which still rely heavily on mouse models despite their limited clinical predictive value.Here, we aim to validate hOss as a superior platform for assessing the efficacy of immunotherapies. Using OssiGel, we will generate hOss and evaluate therapeutic responses, directly comparing outcomes in tumors engrafted in mouse bones versus hOss. Our project addresses a critical need to understand how the human bone/bone marrow microenvironment shapes immunotherapy outcomes. It proposes the first in vivo personalized model for testing immunotherapies, offering insight into the variable clinical success of current strategies.