Immunotherapy has produced durable remissions across a spectrum of malignancies. However, predicting and monitoring therapeutic outcomes remains a challenge. Techniques to achieve these goals without multiple biopsies or other invasive methods will be critical to further improve on immunotherapy. Noninvasive imaging of immune responses is therefore a highly desirable goal. The abundance, movement and expansion of relevant cell types may yield reproducible patterns in responders and nonresponders that could help understand, if not predict, the failure or success of a therapy. To enable noninvasive imaging of the targeted cell populations, we isolated camelid-derived single domain antibody fragments (VHHs) against CD8, PD-L1, CTLA, Class II MHC, and CD11b markers. We also developed a method to site-specifically label VHHs with 18F, 64Cu or 89Zr. Radiolabeled VHHs rapidly clear the circulation (t1/2≈15-30 min) and clearly visualize their targets. Through PET imaging using radiolabeled VHHs, we can monitor and explore patterns of responses in the tumor microenvironment, as such or in response to therapy. Early results suggest that infiltration of a tumor by CD8 T cells may be used as a prognostic criterion. Tumors homogenously infiltrated by CD8-T cells appear more likely to respond than tumors that have heterogeneous CD8-T cell infiltration. Important next questions to be explored by PET imaging include the following. What is the role of regulatory T cells (Tregs) and macrophages? How does the CD8-T cell/Treg-cell ratio change in response to treatment? Is it possible to stratify responders from non-responders soon after starting therapy, and how would this affect treatment strategies? Because the basic methodology proposed here is in principle translatable to a human setting, this approach may ultimately find clinical application.
Citation Format: Mohammad Rashidian, Hidde Ploegh. Noninvasive imaging of antitumor responses as a possible predictive tool [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B080.
- ©2016 American Association for Cancer Research.