Charles Prussak, Pharm.D., Ph.D., Advances in Cell Based Immunotherapies
Charles Prussak, Pharm. D., Ph.D. has over 25 years of experience working in academia and the biotech industry developing cell based therapeutics. Dr. Prussak is currently the Director of the Cell Therapy Translational Laboratory (CTTL), which has been created by the University of California, San Diego (UCSD) to serve as the engine to generate translational cell based therapeutics based on discoveries made in UCSD research laboratories. The CTTL is currently developing TIL and CAR based therapeutics targeted for the treatment of solid tumor cancers and clinical studies employing these agents will be initiated in 2017. Prior to the CTTL, Dr. Prussak founded 3 biotech companies in the San Diego area and has coordinated the generation and production of over 25 biologic products entered into phase I-III clinical studies in the U.S., Europe and Australia. Among the products he has developed include the first commercial gene and cell therapy products enrolled into human clinical trials, the first recombinant oncolytic virus entered into pivotal clinical studies and the first modified cell product for the treatment of Parkinson’s disease.
Recent advances in the clinical development of immune modulating agents targeting PD-1, PDL-1 and CTLA-4 have renewed interest in the potential of cell based therapeutics including those that employ B-, T- and NK-lymphocytes and neutrophils. UCSD and its associated Moores Cancer Center have been at the forefront in the creation and development of these new therapeutic modalities, which are now being advanced into human clinical studies. The Cell Therapy Translational Laboratory (CTTL) under the direction of Dr. Charles Prussak, has been created by the UCSD School of Medicine to serve as the engine to generate translational cell based clinical studies that take advantage of breakthroughs discovered in UCSD research laboratories.
In his presentation, Dr. Prussak will discuss the renewed interest in cell based immunotherapies and the advances his lab is making in creating these next generation therapies. Dr. Prussak is currently developing a chimeric antigen receptor modified T-cells (CARs) that target the fetal antigen ROR1. This ROR1 targeting T-cell CAR is currently in late stage pre-clinical development and phase I clinical studies are expected to be initiated in early 2018.
David Fruman, Ph.D., Dynamic BH3 Profiling identifies novel strategies to enhance leukemia cell killing by venetoclax
David Fruman, Ph.D., is a Professor at UC Irvine where he has been a faculty member since 2000. In 2016 he was elected as a AAAS Fellow. His research interest is signal transduction in lymphocytes, with an emphasis on targeted therapies for blood cancer and immune diseases. He previously served as Associate Director of the UCI Institute for Immunology and is currently the Associate Director of the UCI Cancer Research Institute. He is also co-leader of the Systems, Pathways and Targets program of the UCI Chao Family Comprehensive Cancer Center.
Venetoclax (ABT-199) is a small molecule, cell-permeable compound that selectively blocks the pro-survival function of BCL-2. In 2016, venetoclax was FDA-approved as second-line therapy in chronic lymphocytic leukemia based on dramatic disease control in clinical trials. However, venetoclax has achieved lower remission rates in other leukemia and lymphomas despite high expression of BCL-2 in those tumors. A priority is to identify combinations that enhance the efficacy of venetoclax in these cancers. To address this problem we have used a flow cytometry-based assay known as dynamic BH3 profiling, developed by Letai and colleagues. Dynamic BH3 profiling measures the ability of candidate compounds to increase mitochondrial priming in cells. Compounds that increase priming push cancer cells closer to the death threshold, rendering them more sensitive to killing by venetoclax. Using this strategy we have identified two novel classes of inhibitors that potentiate killing of leukemia and lymphoma cells by venetoclax.
John Nolan, Ph.D., Measurement of Extracellular Vesicles (EVs) by Flow Cytometry: Challenges and Prospects
John Nolan is a Professor at the Scintillon Institute in San Diego, where his lab develops new cytometry instrumentation and applications. He has BS degrees (Biology, Chemistry) from the University of Illinois, a PhD (Biochemistry) from Penn State, and did post-doctoral studies at Los Alamos National Lab (LANL). He was Director of the National Flow Cytometry Resource (LANL), President of the International Society for Advancement of Cytometry (ISAC) and is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE). Recent work from his lab has focused on the development of synthetic nanoparticle probes as labels for cytometry and single particle analysis of extracellular vesicles, including exosomes and microvesicles.
Extracellular vesicles (EVs) are released by most cells and bear molecules from those cells including surface receptors, nucleic acids (including miRNAs), and small molecule metabolites. EVs in biofluids such as blood are expected to be at least as diverse as the cells in blood, and single particle measurements such as flow cytometry are ideally suited to analyze this diversity in principle, but EVs (~100 nm diameter) are 100 times smaller than cells (~10 um) and are expected to bear 10,000x fewer surface molecules and have a 1,000,000x smaller volume. As a result, flow cytometry instruments and methods optimized to analyzes cells are challenged to measure small, dim EVs. However, by judiciously designing instruments, reagents and assays, it is possible to use flow cytometry-based approaches to measure individual EVs. In this presentation I will review the origins and functions of EVs, summarize the challenges for single EV analysis, and highlight approaches for the quantitative analysis of EV diversity.
David Novo, Ph.D., High Dimensional Analysis and Visualization of Flow Cytometry Data
David Novo received his PhD in Biophysics from UCLA. Since then he has been president of De Novo Software, working to guide the development of one of the leading flow cytometry data analysis tools, FCS Express.
The recent explosion in the number of parameters acquired per cell has increasingly challenged the standard approaches (gating and visualization on 1D and 2D plots) of flow cytometry data analysis. A number of high dimensional analysis tools imported and modified from other fields has been applied to flow cytometry data. Instead of alleviating data analysis challenges, this has primarily served to introduce an alphabet soup of algorithmic acronyms to the scientist, each algorithm claiming to be superior to previous methods. Choosing the appropriate tool has never been more difficult. This talk will review the major classes of algorithms in a manner accessible to the non-mathematician , emphasizing the advantages and disadvantages of each approach.