Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
The data presented in this paper shows baseline and on-treatment biomarkers from a phase 1b study of the PD-1 inhibitor nivolumab in renal cell carcinoma. The study examined immune changes in the microenvironment of the tumor, such as types of tumor infiltrating cells and gene expression and show that they correlate with gene expression and protein biomarkers in peripheral blood. The results suggest induction of a Th1 response locally and correlating T cell chemotactic proteins in the periphery, both of which were dose independent.
VentiRx, the developers of motolimod, a TLR8 agonist, have published preclinical and clinical results that indicate effective immune system stimulation in human whole blood cultures, non-human primates, healthy subjects, and late-stage cancer patients. Immune system stimulation in all of these settings is dose-dependent, characterized by similar biomarkers, and consistent with stimulation via the TLR8 pathway. The rapid translation and development of motolimod clearly benefited from the use of standardized immune monitoring systems and validated biomarker assays.
A new paper from Peter Schafer, et al, of Celgene shows how biomarkers can be used to monitor treatment response in an inflammatory disease setting. The early timepoints show a dose-dependent biomarker response while the later timepoints show a more normalized response, possibly correlated with reduced disease severity.