Immunotherapy has shown impressive success in treating several cancers, however, responses to treatment are variable, and predicting the response to therapy remains a major obstacle. Biopsy analyses has correlated good prognosis with infiltration of CD8+ T cells into the tumor and recent preclinical work suggests that tracking of CD8+ T cells in tumors using single domain antibody (VHH)?based PET imaging can accurately predict response to immunotherapy in mice. Furthermore, VHH PEGylation dramatically enhances the sensitivity of this PET imaging. The objectives of this research are to (1) create a VHH specific for human CD8, (2) develop a non-enzymatic, site-specific chemistry to allow for a GMP-scalable dual conjugation of the VHH to a PEG molecule and radioisotope, and (3) validate this reagent for PET-based imaging of human CD8+ T cell trafficking in a humanized mouse model. The successful completion of these objectives will provide the foundation for translation of this innovative technology to a clinical setting as a ?CD8 Scan?, the first of its kind to non-invasively track the human immune system. This technology will become the next standard of care, used in conjunction with immunotherapy to rapidly assess responses to treatment and tailor treatment with the greatest therapeutic benefit.
