Non-invasive quantification of drug-target engagement at the tumor: Lessons from small molecules and biologics
June 4, 2018
- June 4, 2018
Johns Hopkins University CERSI
Tuesday, June 5, 2018
Sridhar Nimmagadda, PhD
Associate Professor of Radiology, Oncology,
Medicine, Clinical Pharmacology, and
Pharmacology and Molecular Sciences
Johns Hopkins School of Medicine
About the Presentation
Knowledge of whether therapeutic agents engage their targets is important for the development of safe and effective treatments. The success of cancer drug therapy depends on a number of factors within the tumor, including how well the drug can infiltrate the tumor and access its cellular target, completeness of drug-target engagement, and the extent of heterogeneity within the cancer cell population. In particular, drug-target engagement, which includes timing and extent of the drug-target interaction, is poorly understood for the majority of anti-cancer therapeutics. Existing technologies such as mass spectrometry assist in the characterization of drug activity in cells and tissues. However, they have limited application in quantifying completeness of drug-target engagement within and across multiple lesions simultaneously, and in real-time. Real-time measurements are important to capture the dynamic changes in tumor target expression, which impacts therapeutic success as is the case for immune checkpoint therapy.
Non-invasive imaging technologies such as positron emission tomography (PET) provide a precise means to quantify drug-target engagement in all lesions concurrently and can be used to address some of the challenges. The application of PET to quantify target engagement and dose-finding of some small molecule therapeutics and biologics discussed. Small molecules targeting chemokine receptor 4 (CXCR4) and antibodies targeting programmed death ligand-1 (PD-L1) presented as case studies.
About the Presenter
Sridhar Nimmagadda, Ph.D. is an Associate Professor of Radiology, Oncology, Medicine, Clinical Pharmacology, and Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine (JHU SOM). He serves as the Scientific Director of the Johns Hopkins Center for Translational Molecular Imaging, a center dedicated to clinical translation of molecular imaging agents.
Dr. Nimmagadda received a Master of Science degree in Chemistry from the Indian Institute of Technology, Madras and a Ph.D. in Cancer Biology in 2005 from Wayne State University/Karmanos Cancer Institute. His Ph.D. studies involved development of nucleoside analogs as proliferation and gene expression imaging agents. His postdoctoral work in the Departments of Radiology and Clinical Pharmacology at JHU SOM focused on translating a nucleoside analog into the clinic and on using radiological methods to understand the distribution of microbicides in female and male genital tracts.
Dr. Nimmagadda’s current research is focused on the development of novel imaging agents for chemokine receptors and immune cell related targets (PD-L1), and the application of those agents to quantify drug-target engagement at the tumor. This work is supported by NIH, DOD and several private foundations. He has authored 55 publications that focus on targeted imaging agent development and applying imaging techniques to characterize tumor biology.