Oncofetal chondroitin sulfates in cancer and cancer immune evasion
Navn på bevillingshaver
Ali Salanti
Institution
University of Copenhagen
Beløb
DKK 300,000
År
2020
Bevillingstype
Research Infrastructure
Hvad?
Using a malaria protein, VAR2CSA evolved to exclusively mediate parasite binding in the human placenta we discovered oncofetal chondroitin sulfate ofCS in 2015. ofCS is a secondary carbohydrate modification present in foetal and placental cells. Later in life it can reappear on almost all malignant tumours. The broad ofCS expression in tumours suggests that it plays an important role for tumour biology. Our results indicate that ofCS is involved in tumour adaption and modification of the extracellular environment. It appears especially important for cancer cell motility and migration. In this project we aim to make a panel of specific antibody reagents to ofCS and use these in vitro and in vivo cancer models to understand the biology behind ofCS expression.
Hvorfor?
Breakthrough technologies has over the last 10 years provided a new line of cancer therapies, called checkpoint inhibitors. These compounds block the negative effect a tumor has on the immune system, and allows immune cells to attack the tumor as was it an infection. However these compounds has only proven effective in a few selected tumor indications. There is an acute need for the development of novel strategies against the vast majority of solid tumors. We have identified ofCS as tumor expressed molecule and we aim to elucidate the role of this molecule in tumor immune evasion and enable targeting using novel immunotherapies based on a recombinant malaria protein.
Hvordan?
The only available reagent to that binds oncofetal CS is the recombinant VAR2CSA protein. The success of our project depends on our capacity to express and purify this protein for our biological studies. The donation from Carlsberg Foundation will enable us to purchase an automated chromatography system enabling us to make high through put proteins. We have also demonstrated that we can make ofCS modified recombinant proteins in human cancer cells, which we can then purify and use for functional studies. In collaboration with researchers at Lund University, using the purified reagents, we will explore the role of ofCS in tumorogenisis and in particular the interplay between cancer associated fibroblasts and ofCS.