Multispecies Comparison of the Impact of Obesity on GVHD/GVT
Description: Currently, allogeneic hematopoietic stem cell transplantation (HSCT) remains as the only curative therapy for the treatment of hematological malignancies. However, its success is dependent on the induction of an immunologically mediated reaction known as graft vs tumor (GVT), which can be complicated by the initiation of adverse events such as graft versus host disease (GVHD) post-transplant. Increasingly, preclinical testing to find therapies to modulate GVHD while maintaining GVT have come under scrutiny for their inaccuracies in predicting patient outcomes in human clinical trials. In this grant application we propose that the discrepancy between preclinical testing and clinical outcomes is, at least in part, due to the vast majority of preclinical testing making use of lean specific-pathogen-free (SPF) animal models which may not be reflective of the real world clinical experience. The CDC currently estimates that more than two-thirds of US adults are either overweight or obese, and therefore we are proposing that the pre-existing inflammatory profiles present obesity are directly correlative to increased risk for GVHD pathogenesis and reduced GVT responses. Accounting for this phenotype in both murine and non-human primate models, we will demonstrate that addition of intervention therapeutics can limit GVHD pathogenesis while maintaining GVT responses within obese models.
Funder: National Cancer Institute
Funding type: research
Funder scheme: R01
Start date: 2017-01-12
End date: 2023-12-31
Investigator: WILLIAM JOSEPH MURPHY
Institution: UNIVERSITY OF CALIFORNIA AT DAVIS
Funded outputs count: 16
Funder award ID: R01CA214048
OpenAlex ID: G6902756509