The field of immuno-oncology is seeing striking successes, yet suffers from ongoing diagnostic challenges that are hampering progress in the development of novel and combination immunotherapies in patients. Non-invasive imaging using PET enables profiling tumor and immune system biology throughout the body. In vivo imaging provides a powerful and complementary approach to in vitro diagnostics, allowing profiling of biology in the context of an intact living organism. Given the challenges of tumor heterogeneity, as well as variability of immune responses, molecular imaging approaches are poised to provide essential information to enhance our understanding of immune responses and immunotherapy.
We have developed engineered antibody fragments to provide a versatile platform for non-invasive imaging of cells and tissues based on cell surface phenotype. Recombinant fragments such as minibodies and diabodies have been developed with accelerated clearance (enabling same-day or next-day imaging), limited or no biological activity (lacking complement/Fc receptor binding), and permitting site-specific conjugation. When labeled with positron-emitting radionuclides (such as I-124, Zr-89, Cu-64, F-18), minibodies and diabodies can be employed for high resolution, sensitive, quantitative imaging by immunoPET and provide highly specific molecular assessments of tumor biology and response to treatment. For example, an I-124 prostate stem cell antigen (PSCA)-specific minibody demonstrates sensitive imaging in mouse models of prostate cancer and provides a PET imaging readout of response to anti-androgens. Antibody-based targeting and imaging of CD markers (CD4 or CD8 on T lymphocytes; CD20 on B lymphocytes) broadens applications to assessment of immune cell subsets and monitoring responses to cancer immunotherapy. A Zr-89 anti-CD8 cys-diabody has been used to detect and image tumor infiltrating CD8+ T lymphocytes in tumor treatment models using anti-CD137 or anti-PD-L1 antibodies, and to detect adoptively-transferred OT-I T cells in mice. Applications extend beyond oncology, with recent visualization of CD4+ T lymphocytes in a mouse model of colitis.
Importantly, immunoPET using engineered antibody fragments can be readily translated, and can provide highly sensitive imaging of cell surface biomarkers in patients. ImmunoPET provides a broad approach for noninvasive, whole-body monitoring of key factors such as target expression in vivo, response to therapy, and immune responses, and stands to play an expanding role in the detection and management of cancer.
Citation Format: Anna M. Wu. Profiling immune cell subsets and immune responses using immunoPET. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA21.