OF-CANCER Team (Oncofetal Glycan)

We have a strong focus on developing treatments or methods that may benefit the individual as well as the society.

Diverse research covering

Understanding the role and fine structure of oncofetal chondroitin sulfate in cancer initiation, progression and metastasis

We have found that basically all malignant tumors express high levels of oncofetal CS whereas only placenta and fetal non-malignant tissues are positive. Our research is focused on understanding how and why cancer cells express ofCS. In particular, we have shown ofCS to play a key role in cellular migration leading to metastasis, but also a critical function in keeping away active CD8 T-cells from the micro-tumor environment.

Clinical development of a radiolabeled anti ofCS antibody for detection of cancer in a wide range of cancer types

We have shown ofCS to be present in all malignant tissue and absent from normal tissue besides fetal tissue. In animal models we see that the antibodies specifically locate to the tumor sites as well as metastasis. Our focus is to show that this is also the case in cancer patients, leading the way for both diagnostics and therapeutics. In collaboration with VAR2Pharma we have developed a Zr89 antibody which we aim to test in human clinical trials.

Diagnosing cancer using detection of oncofetal chondroitin sulfate on circulating cancer cells and in body fluids.

We have found that circulating tumor cells have ofCS on their surface and that we can use VAR2CSA to capture and detect these. This opens up for the possibility to enumerate but also isolate CTCs that would otherwise have gone unnoticed. Similar, we have shown that tumors shed and secrete proteins modified with ofCS and we can capture this as cancer biomarker using VAR2CSA. We are running a number of clinical studies investigating the diagnostic potential. This is in close collaboration with the ofCS biomarker team.

Delivery of drug conjugates in cancer using oncofetal chondroitin sulfate-specific targeting moieties

We have shown that all tumors express ofCS, and that VAR2CSA or Vartumab can be used to target cancer in vivo. This opens for the possibility to use this platform as a stealth seeking misile to deliver drugs to the tumor. We are extensively working on conjugating cellular toxins to VAR2CSA and Vartumab and have shown in key animal models that this provides a very high therapeutic window and full cure of tumor bearing mice. We are working towards translating this to clinical studies.

Development of bi-specific molecules that target oncofetal chondroitin sulfate and engage immune cells

Cancer immunotherapies are attractive as they can initiate an immunological response to the tumor, offering the possibility of full cure with less risk of recurrence. In this project we are fusing VAR2 or Vartumab to anti-CD3, thereby making a bispecific immune-engager. We have demonstrated full curative effect in both allo and xenograft models. The work towards first clinical studies has been initiated.

Development of capsid-based virus-like particle vaccines

Following the initial discovery of VAR2CSA as the malaria molecule responsible for malaria during pregnancy we conducted several phase 1 studies. The work is focused on next generation vaccines on improved antigens and virus like particle display. Similar, we have developed a SARS-COV2 vaccine (ABNCOV2) that has finalized phase 3 development.

Our main focus is translational bioscience in the space between late preclinical development and clinical testing. We have moved several products to early and late clinical stage testing:

1. A VAR2CSA recombinant vaccine expressed in insect cells (phase 1a, 1b)
   
   
2. A VAR2CSA recombinant vaccine expressed in e. coli and presented on virus like particles (phase 1 in planning)
   
   
3. A HER2 cancer vaccine presented on a virus like particle in collaboration with Expres2ion Biotechnologies and AdaptVac (phase 1 in planning)
   
   
4. A SARS-COV-2 prophylactic vaccine where we did phase 1 testing and in collaboration with AdaptVac and Bavarian did phase II and III
   
   
5. Vartumab for a phase 0 imaging trial in collaboration with TRACERCRO and VAR2pharma (phase 0 to commence 2024)
   
   
6. Vartumab for a clinical phase 1 as an ADC (preclinical development, and preparations for phase 1)
   
   
7. VAR2CSA clinical feasibility studies as a cancer diagnostic in collaboration with University Hospital Copenhagen, Køge, Herlev, Hillerød and VARCT Diagnostics

The oncfetal glycan team is working closely together with other CMP research team in the preclinical and clinical development of vaccines and antibody products. The team is engaged in a wide range of national and international collaborations and work closely with university hospitals around the world as well as industrial partners

• Novo Nordisk funded preclinical TANDEM program to target cancer with a bispecific immune engager. Collaboration with Ismail Gögenur from Center for Surgical Science at Sjællands Universitetshospital
• Industrial co-funded project to develop a PET tracer for cancer diagnostic. In close collaboration with TRACERCRO and University of Amsterdam
• Carlsberg foundation funded project to develop a SARS-COV-2 vaccine in close collaboration with Aarhus University, State Serum Institute, Copenhagen University Hospital and AdaptVac
• Collaboration with Vancouver Prostate Centre, University of British Columbia to understand the role of oncofetal CS in cancer through PDX animal models
• Collaboration with University of San Diego to understand the fine structure of onco-fetal CS
• Collaboration with University of San Diego to develop cancer targeting nanoparticals
• Innovation foundation funded industrial collaborations to develop novel cancer targeting agents
• Novo Nordisk funded initiative to understand the role of ofCS in cancer progression and initiation
• A H2020 vaccine program with European Vaccine Initiative to further develop VAR2CSA based vaccines
• EUROSTAR collaboration PURECELL with Xantec and University of Düsseldorf to use ofCS to isolate circulating tumor cells from blood samples for cancer diagnostic purposes.
• PREDICT, a Grand Solution Innovation Foundation funded project in close collaboration with VARCT Diagnostics and three University hospitals to clinical test the developed method on capturing circulating tumor cells for cancer diagnostic purposes.
• Targeting AML with novel drug conjugates and bispecific therapies, a preclinical development project with University Hospital Copenhagen and BRIC.

List of publications by OF-CANCER Team