Researchers developed a method using bispecific single-domain antibodies, called BiCEs, that activate the complement system to target and kill cancer cells more efficiently than current methods. This innovative approach could revolutionize cancer immunotherapy by engaging more of the body’s immune response and has potential for clinical application.
Immunotherapy is a cancer treatment approach that leverages the body’s natural immune defenses to target tumor cells. While much focus has been on engaging T-cells for fighting cancer, less attention has been given to directing the complement system toward tumors.
The complement system is an important part of the innate immune system that helps fight infection, heal injury and remove our dead cells. While antibodies, the proteins generated by our immune cells, can activate the complement system, not all antibodies are equally efficient at activating it.
In the new study, researchers developed a method to activate the complement system using bispecific single-domain antibodies termed BiCEs. These antibodies can bind to two different targets at the same time: a complement protein called C1q and a specific protein present on the surface of cancer cells.
By linking C1q and the cancer cell protein, the BiCE molecules can strongly activate the complement system leading to the specific killing of the targeted cancer cells.
Researchers from the spin-out company Commit Biologics, Christian-Albrechts-University in Kiel and Aarhus University have discovered a new approach to boost the immune system. From left: Steffen Thiel, Annette G. Hansen, Dennis V. Pedersen, Nick S. Laursen, Heidi Gytz Olesen, Gregers R. Andersen & Mikael B. L. Winkler. Credit: Lisbeth Heilesen, Aarhus University
Compared to antibodies currently used in the clinic, the BiCE molecules are even better at activating the complement system and killing cancer cells. The new approach offers several advantages over conventional cancer therapies, one being leveraging the power of the innate immune system to potentially activate a broader immune response, including recruitment of immune cells to the tumor microenvironment for enhanced anti-tumor activity.
The findings of the study not only highlight the innovative research conducted at Aarhus University but also paves the way for further advancements in the field of cancer immunotherapy. Moving forward, the spin-out venture resulting from this collaboration aims to translate the research findings into clinical applications.
Reference: “Bispecific Complement Engagers for Targeted Complement Activation” by Dennis V. Pedersen, Heidi Gytz, Mikael B. L. Winkler, Alessandra Zarantonello, Niklas Baumann, Annette G. Hansen, Steffen Thiel, Gregers R. Andersen, Thomas Valerius and Nick S. Laursen, 23 June 2023, The Journal of Immunology.
DOI: 10.4049/jimmunol.2200952
The company Commit Biologics is a spin-out company from the Department of Molecular Biology and Genetics at Aarhus University.
These guys big brain👍