ImmunoPET of CD38 with a radiolabeled nanobody: promising for clinical translation

Excerpt

Immunotherapy, a therapeutic approach that activates and utilizes a patient’s own immune system, has gathered tremendous attention from both patients and researchers, especially after the 2018 Nobel Prize in Physiology or Medicine was awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.” More than 10,000 studies have been published within the past 2 years for understanding, improving, and clinically translating immunotherapy, based on keyword search in PubMed. For instance, immune checkpoint inhibitors hijacking programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death protein 1 (PD-1), have emerged as the most promising candidates, and several monoclonal antibodies were approved by the Food and Drug Administration (FDA) for treating multiple types of cancer including melanoma, squamous cell lung cancer, renal cell carcinoma, etc. [1]. CD38, a member of the ribosyl cyclase family that is widely expressed on the surface of non-hematopoietic cells and diverse immune cells especially in treatment-resistant tumor microenvironment, has been recently recognized as a novel immune checkpoint protein [2, 3]. Anti-CD38 immunotherapy can be another promising treatment for patients who cannot be cured by traditional methods. However, only a small subset of patients really benefits from immunotherapies, while nonresponders suffer from significant side effects [4]. Therefore, effectively distinguishing responders from nonresponders is a critical challenge confronting the clinicians and scientists, and hence, an area of significant research and innovation. …