After more than four years of intensive research, SciLifeLab Group leader, Sara Mangsbo (Uppsala University), and her immunotherapeutic cancer vaccine delivery-platform, is ready to leave the SciLifeLab Drug Discovery and Development platform (DDD).
The platform is based on a new technique, called Adaptable Drug Affinity Conjugate (ADAC), that can help our immune system to detect “invisible” tumors and mount an attack against them. This is achieved by letting antigen presenting dendritic cells (DCs) present tumor specific antigens, identified from patient tumor samples, to activate T-cells, enabling them to identify and attack the tumor.
“It is inspiring to see something so innovative being born in Sweden,” says Kristian Sandberg, head of the DDD platform, in a news article from Uppsala University.
Immunotherapy is a rapidly growing field, aiming to utilize and strengthen our immune system so that it more easily can find and kill tumor cells. Antibody-Drug Conjugate (ADC), is a known method that relies on injecting cancer specific antibodies equipped with cytotoxic drugs that can be delivered straight to the tumor cells.
Another approach, based on ADC, is to replace the cytotoxic drugs with tumor specific peptides, obtained from patient samples, and target antigen presenting cells instead, in order to boost and activate the immune system against the tumor. The problem with this approach, however, is the lack of an effective delivery system, capable of delivering the unstable peptides to the right antigen presenting cells (APCs).
In the latest SciLifeLab DDD-project, SciLifeLab researcher Sara Mangsbo and her team, have created a new method (ADAC) to overcome this problem, making the strategy far more effective and cost-efficient. With the new method, the body can be turned into a T cell factory, generating a custom made, coordinated attack on the tumor. The newly created tumor specific T cells can then alert the immune system which in turn can activate already existing T cells and recruit them in the fight.
“Immunotherapy is riding on a wave of success, but still faces the challenge of increasing the body’s number of tumor-specific T cells and getting them to seek out and destroy the cancer cells. We have chosen a partly alternative strategy and developed a method reminiscent of vaccination, where we, through an injection, make the tumor visible to the immune system and accelerate the production of the specific T cells required”, says Sara Mangsbo, in the news article.
The research team have designed a new CD40-based tetravalent bispecific antibody linked to an anti peptide tag that holds the synthesized peptide chains. When the antibodies bind to, and activate dendritic cells, the peptides become internalized and can be presented to the T cells. This design has been shown to provide optimal stability for the peptides as well as successfully deliver them to the dendritic cells where they subsequently activate the T cells.
The team has also been collaborating with Testa Center, an innovation environment and test bed located at Cytiva’s site in Uppsala, to make the necessary preparations following clinical trials. Here, they have access to high-quality equipment and expertise on upscaling biological processes, which makes it possible to test the potential of the new delivery system at an early stage. They were also able to investigate important factors like production and purification processes, and the stability of the antibody.
Now, the researchers will continue to develop the method within the framework of the newly started company, Strike Pharma AB, in which they unite researchers from Uppsala University and KTH, among others. Strike Pharma AB is located in the Green Innovation Park, an innovation environment at the Swedish University of Agricultural Sciences, with a focus on cooperation, innovation and sustainable innovations.
“We believe that it is the right environment for us to take the next step regarding the design and production of the specific antibody that we have developed. If we reach our goal it can lead to a significantly shorter path to cancer treatment, but we have also identified great potential concerning outside cancer. In Strike Pharma AB, we muster a very competent line-up and have the funding to take us a long way, so the future definitely looks promising”, says Sara Mangsbo.
Photo: Mikael Wallerstedt