PI: Dr. Roland Strong
Location: Fred Hutchinson Cancer Research Center
Tailoring immunotargeting and immunomodulatory reagents for the treatment of cancer
This project builds on two ongoing efforts: (1) to specifically elicit, customize and weaponize antibodies to target solid tumors induced by viruses and (2) to translate immunomodulators that target T cell co-receptor signaling pathways from canine to human patients for managing the sequelae of treatments for hematopoietic tumors. Antibodies are clinically-relevant reagents for treating various diseases, though often require chemical conjugation to generate useful diagnostics or therapeutics. We are developing novel antibody fusion proteins, adding functional modules that enable simple, plug-and-play, non-covalent incorporation of a variety of adducts. We are also developing improved versions of MHC proteins as immunogens to efficiently elicit antibodies specific for virally-infected cells. Computational refinement of initial designs is required to fully realize these approaches. Bone marrow transplants, now embodied as non-myoablative hematopoietic stem cell transplants (HSCT), are highly effective in the treatment of leukemias, but often result in potentially fatal graft-versus-host-disease (GVHD). We are developing improved immunosuppressive regimens based on engineered ligands for T cell co-receptors that would reduce the often debilitating side-effects of current protocols, using the dog model of post-HSCT GVHD. Computational reengineering will be required to translate canine-specific reagents to the human system while minimizing immunogenicity. Both applications are active collaborations with clinicians.