Cancer is projected to cause well over half-a-million deaths in the US in 2015, and is expected to surpass heart diseases as the leading cause of death in the next few years. While T-cell-based immunotherapy holds great potential to cure cancer, there are multiple roadblocks including therapeutic effectiveness, patient individuality, biomanufacturing, and cost. This proposal aims to tackle these limitations by making nanoscale assemblies of proteins that can collectively program a patient's own immune system to seek out and destroy the cancer cells. The modular nature and the inexpensive production system of the protein assemblies hold promise to make personalized cancer immunotherapy both effective and affordable. The successful completion of this work will provide an enabling strategy for developing personalized immunotherapy to treat cancer and help define the metrics of effective anti-tumor immune cell responses.

T-cell based immunotherapy holds great promise to treat cancer, as recognized by the recent approval of sipuleucel-T to treat advanced prostate cancer. The key to a successful T-cell immunotherapy is to elicit a potent anti-tumor response by presenting the right signals (i.e. protein ligands) in the right spatial pattern to T cells as observed in the immunological synapse. While artificial presenting systems represent an affordable alternative to adoptive transfer of patient's own immune cells, their existing designs lack the spatial control of the protein ligands, resulting in limited beneficial clinical outcome. The investigator proposes a novel approach of synthesizing tunable and scalable protein assemblies (TSPAs), which consist of multiple T-cell-activating protein ligands of choice that self-assemble into defined supramolecular patterns on an addressable scaffold. Coupled with high dimensional single-cell phenotyping, the availability of the proposed TSPAs opens up the possibility to engineer personalized and affordable immunotherapy. Specifically, using breast cancer as a model system, the investigators will establish the relationship between the composition of the T-cell-activating ligands in the TSPA, the pattern of the ligands, and the anti-tumor activity of the activated T cells. This will further enable the identification of the optimal TSPA configuration to mount an effective anti-tumor T-cell response. The successful completion of this work will provide an enabling strategy for developing personalized immunotherapy to treat other types of cancer, and help define the metrics of effective anti-tumor T-cell responses. The definition of such a standard will significantly improve the ability to predict T-cell therapeutic outcome and help provide guidelines for designing better cancer therapeutics and vaccines. To generate a broader impact, protein and life science research-based learning platform will be established at different academic levels to foster students' interest in engineering and manufacturing therapeutic molecules, increase their knowledge in the emerging field of personalized medicine, and provide new opportunities for women and underrepresented minorities to pursue careers in engineering and medicinal science. These efforts will collectively help create a new generation of engineers with a multi-disciplinary skillset ready to make an impact on human health.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Regents of the University of Michigan - Ann Arbor
Ann Arbor
United States
Zip Code