Speaker: Cheng Dong, Pennsylvania State University

CAR T cells mediated delivery of clickable biodegradable nanoparticles to brain tumors

Abstract:

Efficient drug delivery strategies into solid tumors that target primarily malignant cells and avoid damaging healthy tissue are limited by the pharmacokinetics, solubility and specificity of the chemotherapeutic drugs. Drug delivery into brain tumors is significantly more challenging due to the presence of the blood brain barrier. Glioblastoma, with a 5-year survival rate of only 5% is the most aggressive type of brain tumor. Despite modern treatment techniques (e.g. chemotherapy, radiation, and surgical removal), the prognosis remains dismal. To address this clinical challenge, we designed a targeted drug delivery system using genetically modified chimeric antigen receptor (CAR)-T cells expressing high-affinity mutant Interleukin-13 to target glioblastoma tumors and polymeric nanoparticles to encapsulate the therapeutic drug. Nanoparticles provide a great opportunity to develop a targeted delivery system that in conjunction with immune cells can specifically deliver drugs to brain tumors.

Biography:
Professor Dong received his M.S. (1984) and Ph.D (1988) from Columbia University, co-mentored by Professor Richard Skalak (Civil Engineering & Engineering Mechanics) and Professor Shu Chien (Physiology, P&S). He is now a Distinguished Professor of Biomedical Engineering and Head of the Penn State Department of Biomedical Engineering.

Prof. Dong is currently a Member of the United States National Committee on Biomechanics (USNCB); a Fellow of the Biomedical Engineering Society (BMES); a Fellow of the American Institute of Medical and Biological Engineering (AIMBE); a Council Member of the International Society of Biorheology (ISB); a past Chair of the BMES Cellular & Molecular Bioengineering (CMBE) Special Interest Group (SIG); and a past Secretary of the national Biomedical Engineering Council of Chairs (CoC). He is a Member of the American Association for Cancer Research (AACR) and the American Physiological Society (APS). Dr. Dong is also a Managing Editor for Frontiers in Bioscience; an Associate Editor for BMES Cellular and Molecular Bioengineering; and an Associate Editor for Molecular and Cellular Biomechanics; as well as an Editorial Member of the Chinese Journal of Medical Biomechanics. Prof. Dong was a recipient of the NSF Faculty Career Award; American Cancer Society Faculty Research Award; ASME Y.C. Fung Young Investigator Award; ASME Melville Medal; ASME Best Journal Paper Award; and BMES Harold Lamport Young Investigator Award.

The major focus of Dr. Dong's research is to elucidate biomechanical, biophysical and biochemical aspects of cellular function in the circulatory systems, with particular interest in cell adhesion, cell migration, cell signaling, cellular biomechanics and multi-scale modeling of biological systems. Current research at Penn State University includes studies of micro-hemodynamics, coagulation, leukocyte rheology, intercellular and intracellular signaling, cancer immunology and metastases. In particular, he is investigating how fluid dynamics, adhesion kinetics and tumor microenvironment change leukocyte and/or endothelial immune functions which subsequently affect tumor cell extravasation in the microcirculation and subsequent metastasis. He is also collaborating with material scientists and neural science biologists on most-recent designs of immune cell-mediated nanoparticle and drug delivery targeting brain tumors.