Next Generation Genetic Discovery Systems in Human Immune Cells

Explore cutting-edge genetic discovery technologies for engineering human immune cells in this 31-minute webinar presented by Dr. Theodore Roth from Stanford University. Learn about the development and application of Modular Pooled Knockin Screening (ModPoKI), a revolutionary platform that enables rapid association of large pools of T cell genetic modifications with high-dimensional single cell phenotypes across diverse cancer immunotherapy contexts. Discover how this scalable technology addresses the current limitations of engineered immune cell therapies, particularly in solid tumor treatment, by providing effective methods to directly compare large numbers of potential clinical constructs. Examine the construction of libraries containing transcription factors and natural and synthetic surface receptors, including numerous constructs under clinical investigation. Understand how over 20 ModPoKI screens across dozens of healthy human donors in both TCR and CAR T cells generated a comprehensive genotype-phenotype map that benchmarked existing clinical constructs and identified novel cell therapy targets capable of overcoming cancer resistance mechanisms. Gain insights into the identification of transcription factor AP4 (TFAP4) as a construct that enhances long-term T cell fitness and anti-cancer function, and learn about the unexpected functional relationships discovered within CAR T cells through synthetic transcriptional programs. Explore how non-viral knockin of combined BATF-TFAP4 polycistronic constructs further enhanced in vivo function, demonstrating ModPoKI's potential to facilitate scalable discovery of complex gene constructs for programming improved engineered immune cell functions tailored to specific cancer resistance mechanisms.