Next generation immuno-oncological targets for cancer therapy

The focus of this project is bladder cancer where patients with tumors that have grown into the underlying muscle (i.e muscle invasive disease) have a 5-year survival of only 50%. Patients with less advanced disease have a better survival (around 85% 5-year survival), but recurrences are very common and around one in five will later be diagnosed with muscle-invasive disease [1]. Despite that bladder cancer have characteristics generally associated with response to the main I-O treatment, using checkpoint blockade, only around 15-30% of patients respond to the treatment [2,3]. The overall aim of the project is to identify and exploit novel drug targets that enable the immune system to efficiently eradicate cancer cells.

The research group has already created an atlas of the immune cells infiltrating bladder tumors, based on single-cell RNA sequencing. Specifically, the distinct transcriptional profiles of the infiltrating immune cell populations have been defined and these profiles indicate selective expression of various surface markers. The transcriptional data will be used to pinpoint candidate surface targets on the infiltrating immune cells, that can be used to manipulate the immune response and trigger tumor cell elimination. The identified immune cell populations and candidate targets will be evaluated using e.g. multiplex flow cytometry, spatial proteomics and in vitro assays. Against promising targets, tailored antibodies will be developed and assessed functionally. Based on Sarah’s expertise, we aim to develop an ex vivo tumor culturing model with fresh clinical samples, for functional evaluations of targets and antibodies.

References

1. Patel, V. G., Oh, W. K. & Galsky, M. D. Treatment of muscle‐invasive and advanced bladder cancer in 2020. CA. Cancer J. Clin.70, 404–423 (2020).
2. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. doi:10.1126/science.aar4060
3. Zang, J. et al. Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis. Front. Oncol.11, 1–13 (2021).