Abstract: Chimeric antigen receptors (CARs) are synthetic modular proteins that allow for directing immune cell reactivity towards a molecular target of interest, such as a cancer-associated antigen. CAR-T cells have demonstrated remarkable clinical activity in patients with refractory hematologic malignancies, leading to six FDA-approved products to date. There is much hope that next-generation platforms leveraging synthetic biology and genetic engineering will expand this class of therapeutics to solid tumors, where toxicity risks and limited efficacy are major barriers to progress. However, current platforms for enhancing CAR potency are at risk for increased toxicity, while those that are designed for safety exhibit diminished potency. In the first part of my talk, I will present on SNIP, an extensively optimized CAR ON switch that dually enhances safety and efficacy of T cells and is regulated by an FDA-approved small molecule. SNIP CARs outperformed conventional CARs in numerous solid tumor models. Through phenotypic and functional studies, we show that the enhanced activity of SNIP CARs is due to diminished T cell exhaustion and greater generation of memory T cells. In order to meet the multiple obstacles facing CAR-T cells in solid tumors, next-generation smart therapies need to be multi-specific, resistant to exhaustion, and maintain their fitness in a hostile tumor microenvironment. Engineering NextGen therapies with these enhanced capabilities will require the introduction of additional genetic modules that often do not fit within the payload capacity of a single vector. In the second part of my talk, I will introduce STASH Select, a simple platform technology for enriching cells that have been engineered with multiple vectors using a single-step selection that results in high purity/yield and is compatible with current cell manufacturing workflows and closed loop systems.
Bio: Louai Labanieh, PhD, is a postdoctoral research fellow and Parker Institute for Cancer Immunotherapy Scholar at the Stanford Cancer Institute. He completed his PhD in the Department of Bioengineering at Stanford University. Dr. Labanieh has an overarching goal to leverage immune engineering and synthetic biology to develop curative therapies for cancer that are broadly accessible to patients. As a clinically oriented bioengineer, he has developed several platform technologies for improving the safety and efficacy of engineered T cells that are optimized for the clinic, including the SNIP system which is currently in development for a clinical trial in refractory solid tumors. He is an inventor of over a dozen technologies, which are at various stages of commercialization by startup or publicly traded biotech companies. He has authored 25 publications in top-tier journals in the areas of CAR-T cell therapy, synthetic biology, immunology, protein engineering, and nucleic acid-based biosensors. His work has been recognized by multiple awards including the PICI Scholar, Siebel Scholars Award, EDGE Diversity Fellowship, NSF Graduate Research Fellowship, and Stanford Graduate Fellowship. Dr. Labanieh was recently chosen to speak at the 2023 Stanford. Berkeley. UCSF NextGeneration Faculty Symposium in recognition of his research accomplishments and demonstrated contributions to enhancing diversity, equity, and inclusion in STEM.