User : Molecular Targeting Technologies Inc.
Approximately 94% of patients with small cell lung cancer (SCLC) are diagnosed with metastatic, which has a 5-year overall survival rate of only 2%. Chemotherapy and radiotherapy are the primary treatment options for these patients, highlighting a critical unmet clinical need. Somatostatin receptor II (SSTR2) is overexpressed in 55–70% of SCLC cases.
We have developed a therapeutic radiopharmaceutical, [225Ac]Ac-EBTATE, which has demonstrated effectiveness in preclinical models of SSTR2-positive SCLC. However, complete tumor remissions have not been observed in all treated mice. Emerging preclinical and clinical evidence suggests that radiation can modulate and prime the tumor immune microenvironment, potentially enhancing therapeutic outcomes when combined with immune checkpoint inhibitors (ICI).
This project aims to investigate whether this is the case for SCLC by utilizing single-cell RNA sequencing (scRNA-seq) to analyze changes at the protein and genomic levels in the TME before and after treatment with [225Ac]Ac-EBTATE. We will then evaluate the therapeutic benefits of combining [225Ac]Ac-EBTATE with ICI, such as atezolizumab, in syngeneic mouse models bearing SSTR2-positive SCLC tumors. The findings will be crucial for designing a clinical trial combining [225Ac]Ac-EBTATE with ICI for SCLC. This approach has the potential to improve treatment outcomes for SCLC and deliver significant socio-economic benefits to the province.