Assessing CD36 and CD47 expression levels in solid tumor indications to stratify patients for VT1021 treatment

Abstract Cancer is one of the leading causes of death worldwide. While there are a multitude of cancer treatments, both approved and in clinical trials, there is still a critical need for therapies that are developed for more targeted populations. Despite the development of novel cancer biomarkers and target therapies currently in use, most cancer patients do not have a specific biomarker directly associated with effective treatment options. We have developed VT1021, a cyclic peptide that induces the expression of thrombospondin-1 (TSP-1) in myeloid derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). TSP-1 reprograms the TME via binding to CD36 and CD47 to induce tumor and endothelial cell apoptosis as well as reprogramming of the tumor immune microenvironment (TIME). VT1021 has finished a Phase I trial and is currently being tested in a Phase II/III clinical study in glioblastoma (GBM). In this report, we analyzed the expression signature of CD36 and CD47, the major receptors for TSP-1, in patients' tumor cells from the VT1021 Phase I trial and identified that this signature could be used to stratify patients and predict response to VT1021 treatment. We also found that CD36 and CD47 were elevated in multiple solid tumor indications through tissue microarray (TMA), providing further evidence to support using CD36 and CD47 as biomarkers in other types of cancer. Finally, we validated the CD36 and CD47 expression signatures, using annotated clinical data from the National Cancer Institute (NCI) Genomic Data Commons (GDC) Data Portal. Our studies identified CD36 and CD47 as dual biomarkers that can be used as patient stratifying tools and prognostic biomarkers for multiple cancer indications. Patients with dual high levels of CD36 and CD47 expression in tumor cells would benefit the most from the VT1021 treatment.