Research group The research is focused on elucidating information released in to the circulation and how to decode the information into personalized medicine approaches. This include identifying novel liquid biopsy platforms to access tumor derived information to identify early cancer, predict outcome, and monitor therapy response in a non-invasive fashion.
Another research focus relates to the interaction between cancer cells and their microenvironment, and how the tumor can circumvent the immunosurveillance, called immune editing, and the new line of immunotherapies directed against them, e.g. check-point inhibitors. There we aim enhance the body’s own healing capacity by reactivating the immune system. There are two arms on this research project, one directed at the priming of the T-cells and increase the number of tumor-killing T-cells via neoantigen presentation by antigen presenting cells. The second arm are directed more against the immune exclusive barrier around so called “cold” tumors, breaking it up and promote invasion of tumor-killing immune cell.
Our group have a translational science approach driving projects to personalize cancer medicine and decipher tumor information into actionable knowledge.
One study which have had an impact was our “proof-of-concept” study on extracellular vesicles (microvesicles / exosomes) released from the prostate tumor into the urine to identify classical prostate biomarkers.
This proof-of-concept study was further developed by collaborators (Dr. Johan Skog, MGH, Boston, US).
Nilsson et al. 2009 BrJCa DOI: 10.1038/sj.bjc.6605058
Next step into the liquid biopsy field was made by the move to VUmc, Cancer Center Amsterdam, and Prof. Wurdingers lab, where we set out to find alternative biomarker sources in the blood circulation. In this project we identified platelets as carriers of information, both in an uptake manner as well as through tumor education of platelets.
Nilsson et al. 2011 Blood DOI: 10.1182/blood-2011-03-344408
Best et al. 2015 Cancer Cell DOI: 10.1016/j.ccell.2015.09.018
Patient stratification and response monitoring in mCRPC and NSCLC. Using information released from the tumor cells we aim to identify biomarkers that can be used for therapy selection and longitudinal monitoring of therapy response in a minimal invasive fashion (e.g. blood samples). For that we have developed platforms for biomarker monitoring both within circulating-free DNA, in tumor-educated platelets and from circulating tumor cells (CTCs).
In recent years the molecular understanding of therapy resistance in castration resistant prostate cancer have evolved along with novel therapies and new techniques to follow genetic alterations in the blood circulation, so called “liquid biopsies”. The new therapies come with a high cost and a burden to the healthcare system and tumor heterogeneity limits the number of patients responding to specific treatments. Therefore, therapies need to be accompanied by a diagnostic test that identifies responders from non-responders and helps guiding personalized therapy stratification.
To accomplice this, new circulating biomarkers need to be found that can be used upfront to predict response and to monitor therapy resistance. In this project we use tumor-derived RNA information in platelets to identify molecular aberrations predictive of tumor vulnerabilities that can be exploited. Furthermore, we develop unique tumor educated platelet profiles for identification of molecular subtypes of prostate cancer and investigate the use of these profiles in liquid biopsies to predict and follow therapeutic outcome of standard treatments.
There are three important ways of reducing mortality caused by lung cancer; foremost is prevention, e.g. don’t smoke, secondly is to detect cancer early when we can cure it, and the last resort is to personalize therapy and follow changes in the tumor in real-time to adapt the therapy upon therapy resistance.
This project focuses on developing a personalized cancer monitoring program for lung cancer patients. We will explore the feasibility of personalized biomarkers for patient monitoring, using genetic profiling of tumor tissue and circulating tumor DNA. The platform “Umeå Molecular Adaptive Platform (UMAP)” will enable development of a personalized liquid biopsies workflow using genetic biomarkers. The strength with UMAP is the combination of fast and nimble ddPCR-based assays for monitoring tumor burden and personalized NGS hybrid-capture based deep sequencing for identification of acquired therapy resistance.
With this project we aim to provide a robust clinically implementable workflow to enable personalized biomarkers in liquid biopsies for rapid monitoring of tumor burden and acquired resistance, to always be one step ahead of the cancer and therefore reduce the lung cancer mortality.
SC-FACS-RNAseq of Circulating Tumor Cells (SCTCseq):
One way of collect complete tumor information is to isolate CTC from the blood of the patients, however it is complicated by the scarcity of CTCs (a few tumor cells per millions of normal cells). In this projct we have developed a novel method that can isolate pure CTCs from a blood sample and isolate intact RNA and DNA from the cells. This enable single cell information from the tumor that will help us understand the driving force behind progression and determine the heterogeneity of the cancer.
With the rise of the immuno-oncology research field and with therapies that can cure advanced cancer the fourth therapeutic modality are now implemented and has rapidly taken a central position in cancer managements. Immune checkpoint inhibitors (ICI) (therapies directed against CTL4/PD1/PDL1) are now considered standard options for many cancer indications. However promising ICI are only effective within a subpopulation of cancer patients. This have pointed out the need for development of immune modulatory therapies or immune booster approaches that increase the efficacy of ICI therapies.
One of the problems with ICI resistance is the prevention of immune effector cells (mainly cytotoxic T-cells) to infiltrate the tumor area to target the tumor cells (a.k.a. immunological “cold” tumors), and recently anti-angiogenic therapies (e.g. anti-VEGF) has been used to normalize the tumor vasculature leading to an increased immune cell infiltration and increased cytotoxic effect potentiating the ICI therapies (heating up “cold” tumors). In our research we have identified a new immune boosting candidate, the Adrenergic Receptor Beta family.
Today, there are no approved drugs against our target and we therefore aim to developed novel chemical compounds inhibiting catecholamine activation of our target receptors.
We are developing a new method for generating personalized therapeutic RNA vaccines through enrichment of a specific pool of RNAs modified by the tumor. The modifications are key features when it comes to translation of novel neoantigens which allow rapid isolation a neoantigen enriched pool of RNAs that can be delivered back as a personalized therapeutic cancer vaccine. One strength of the present technology is the diversity in the neoantigen composition, with our approach providing a broad range of neoantigens that can be present at the same time to the immune system. Since mRNA vaccines has shown promise to induce potent immune responses, our enriched RNA population should do the same as well. Preliminary data suggests that our technology of tumor RNA enrichment and subsequent vaccination induce an immune response.
Collaborators: Mattias Forsell (UmU)
Spin-off: Circular Biotech AB