The Award was presented to Transgene and BioInvent at the annual Society for Immunotherapy of Cancer (SITC) conference from 8 to 12 November 2022 in Boston (USA). Entitled Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject ‘cold’ tumors (https://pubmed.ncbi.nlm.nih.gov/35058324/), the first two co-authors are Monika Semmrich (PhD), Principal Scientist at BioInvent, and Jean-Baptiste Marchand (PhD), Head of the Protein Science Lab at Transgene.
Their research related to the impact of the BT-001 oncolytic virus on the treatment of solid tumors.
Transgene, a biotech company based in Strasbourg, eastern France, has been specializing in new cancer therapies since the 2000s. Its pipeline currently consists of 4 immunotherapy products in clinical trial (2 therapeutic vaccines and 2 oncolytic viruses).
Oncolytic viruses are attenuated and modified viruses used as vectors to entrain the immune system. They reproduce themselves in cancer cells but not in healthy cells.
They will spread in these cancer cells and kill them. Moreover, as a result of a gene previously introduced into their DNA, they will be able to induce the production of a powerful drug only in the tumor “which limits the exposure of the other organs and consequently reduces side effects to a minimum,” said Hedi Ben Brahim, CEO of Transgene. Finally, pre-clinical research has shown that the death of the cancer cells activates the immune system overall. BT-001 transforms “cold” tumors into “hot” tumors, which are then detected and attacked by the immune system.
The “Trojan horse” virus contained in BT-001 is well known and very safe as it is the vaccine used for smallpox vaccination. It was modified specifically to attack cancer cells, by suppressing genes and thus making its replication deficient.
“This award by the JITC constitutes a major recognition, which testifies to the quality of the Transgene and BioInvent development and research which led to BT-001. We are very proud of the substance of this research and the form of the article,” Hedi Ben Brahim, CEO of Transgene.
The JITC article rewarded the pre-clinical trials carried out on mice with two tumors. Only one tumor was injected. It was shown that all the injected tumors reduced in size and disappeared completely in 20 days, and 8 times out of 10, the second tumor also became smaller.
BT- 001 is the result of the first collaboration between Transgene and BioInvent. The DNA of the virus contains a drug and a monoclonal antibody with a well-known mechanism of action, the anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4). This drug exists already on the oncology market, but has numerous side effects. “By attacking cancer cells, the system may become too aggressive and lead to auto-immune diseases,” said Hedi Ben Brahim. “Our aim is therefore to use the full force of this drug while reducing its side effects to a minimum.”
BioInvent specializes in this type of drug. The Swedish company has created a new anti-CTLA4 and Transgene has put it in its virus, thus taking advantage of the best of both companies.
Transgene has a proprietary development platform for drug candidates, Invir.IO. The biotech company can thus design not only its own products but also those of outside companies. It is currently developing five products on behalf of AstraZeneca, which also took a license on one of the products in 2021.
Transgene and BioInvent are in the process of completing the monotherapy phase. In 2023, BT-001 will be combined with MSD’s pembrolizumab, a reference drug in oncology.
