UCSF Center for Synthetic Immunology: Tools to Reprogram the Immune System to Combat Cancer
The immune system has emerged as an extraordinarily powerful tool for combating cancer. One of the most
potent agents are engineered T cells programmed to recognize and kill tumor cells. Nonetheless, our ability to
engineer T cells and other immune cells and program them to execute new functions remains relatively primitive.
Aside from CAR T cells for treatment of blood cancers, most engineered cell therapies are risky, potentially highly
toxic, unreliable and often ineffective, especially those cell therapies that attempt to target solid cancers. We
hypothesize that to fulfil the promise of engineered immune cell therapies, we must first transform cell
engineering into a systematic and predictable process; one that uses reliable technology platforms and
principles. Our center will focus on developing a set of sophisticated immune engineering platforms that address
three major needs in next-generation cell therapies:
1) Smart recognition of cancer – develop antigen-pattern recognition circuits that direct immune cells to
optimally recognize solid tumors and discriminate against normal tissue crossreaction, guided by
computational bioinformatic analysis of gene expression patterns.
2) Overcoming the tumor microenvironment – develop multiple classes of cellular circuits that can overcome
or locally remodel immune-suppressive tumor microenvironments to promote highly efficient therapeutic
immune cell trafficking, proliferation, persistence, and tumor-killing activity
3) User-control and safety – to increase control over and safety of these powerful engineered cells, we will
develop a suite of ways to communicate with and control the activity of engineered immune cells in vivo,
including nano/microparticles and small molecules.
To achieve these goals, we have assembled the UCSF Center for Synthetic Immunology, a tightly integrated
interdisciplinary team that encompasses synthetic biologists, immunologists, bio-informaticists, control
engineers, and materials scientists. The products of this center will include publicly available toolkits of parts
and circuits for cell engineering, high-throughput platforms for rapid circuit assembly, new programmable
nanomaterials for controlling immune cell behavior, searchable bioinformatic databases for optimization of tumor
recognition, and computational frameworks for circuit design and for modeling/prototyping in vivo circuit function.
These platforms will help to advance immune cell engineering to be far more reliable, predictable, effective and