International collaboration explores organoid models to predict chemotherapy toxicity

An international collaboration is set to use patient-derived organoids to better understand and predict off-target toxicity from chemotherapy drugs, with the aim of improving safety in cancer treatment.

The initiative brings together iXCells Biotechnologies, Rosebud Biosciences, Kantify, and Incite to develop human organoid models of heart, liver, and kidney tissue for evaluating chemotherapeutic compounds. Funded by Incite, the project will focus on generating personalised toxicity profiles that could help inform future treatment strategies.

At the centre of the study, iXCells Biotechnologies will reprogram patient-derived peripheral blood mononuclear cells (PBMCs) from a liposarcoma patient into induced pluripotent stem cells (iPSCs). These cells will then be differentiated by Rosebud Biosciences into heart, liver, and kidney organoids using its 3D organoid platform, enabling multi-organ toxicity testing of experimental cancer therapies provided by Kantify, which applies its Sapian AI engine to drug discovery.

Toxicity responses will be assessed using a combination of longitudinal imaging, machine-learning analysis, cardiac functional measurements, viability assays, immunocytochemistry, and multiparametric readouts of tissue injury and dysfunction.

Chemotherapy-induced damage to vital organs remains one of the major limitations in cancer treatment, contributing to clinical trial failure and dose-limiting toxicity in patients. By testing drugs directly in patient-derived organoids, the collaboration aims to more accurately model individual responses and reduce the risk of unforeseen adverse effects.

Steve Smith, CEO of iXCells Biotechnologies, said: “This collaboration demonstrates how hiPSC technologies and organoid systems can transform precision toxicology. By starting from a patient’s own cells, we gain unprecedented insight into off-target toxicity, one of the biggest challenges in developing safer and more effective cancer therapeutics.”

Kitch Wilson, CEO and Co-Founder of Rosebud Biosciences, added: “This project is addressing one of the most urgent questions in oncology, determining whether a patient’s vital organs can tolerate life saving therapies. By combining our scalable organoid technology with iXCells’ expertise in cellular reprogramming and Kantify’s AI drug discovery platform, we are creating a patient specific testing system for novel chemotherapy drugs that reflects exactly the type of new approach methodologies the FDA is encouraging.”

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