Development of specific immunotracers against CD8 and/or CD69 for non-invasive imaging of immune responses during anti-cancer immunotherapy

Immunotherapy is a type of cancer treatment that uses the patient's own immune system to recognize and kill malignant tumor cells. Many types of immunotherapies have been developed with generally favorable outcomes. However, not all patients benefit, and side effects vary greatly. Thus, there is an unmet need for a personalized approach. Currently, blood and tissue biomarkers are used to assess the patient's responsiveness to immunotherapy. However, these techniques are invasive and only provide a snapshot assessment. Non-invasive whole-body imaging of the patients' immune system could resolve these issues and result in more personalized immunotherapies.

Within this research proposal, we will develop novel monovalent nanobody-based PET tracers targeting human CD69 or CD8 for nuclear imaging of activated immune cells or cytotoxic T lymphocytes, resp., key players during immunotherapy. Moreover, we will develop a first-in-kind bispecific immunotracer by conjugating nanobodies against CD8 and CD69, thereby aiming to improve selectivity towards activated cytotoxic T lymphocytes. These tracers will be generated and characterized extensively in vitro and in vivo. Moreover, we hypothesize that we can non-invasively visualize and track these different immune cell populations in mice and non-human primate models during (cancer) therapies. These tracers could provide a basis for improved patient stratification during (immuno)therapy.