New Anti-Interferon Antibodies Developed by Wistar Team for Future Therapeutic Candidates

Scientists from the Wistar Institute report that they have isolated and cloned fully human antibodies that can block specific Type-I interferon (IFN) molecules in vitro. Their discovery has an array of potential clinical and research applications, enabling scientists with a new way to investigate the role of specific Type-I interferons in a variety of diseases, according to the Wistar team.

The study “Cloning and functional characterization of novel human neutralizing anti-interferon-alpha and anti-interferon-beta antibodies” appears in the Journal of Immunology.

As an immunomodulating subtype of cytokine Type-I IFNs help the immune system combat disease, cancer, and viral diseases. Type-I IFNs include several specific IFNs that can aid in the modulation of how immune systems respond to infection, but when they become dysregulated or over-expressed, they can also contribute to shutting down the immune system. In HIV infections, Type-I IFNs have been observed to produce paradoxical effects, working for and against the virus simultaneously.

Due to the complexity and ambiguity of how best to therapeutically target IFNs’ broad effects on immune control, scientists in the laboratory of Luis Montaner, DVM, DPhil, sought to develop several antibodies to target and selectively block two major but distinct Type-I IFNs: interferon alpha (IFN-α) and interferon beta (IFN-β). First author Emmanouil Papasavvas, PhD, and his collaborators sought to take advantage of the body’s natural immune response in persons receiving IFN-α or IFN-β treatment, as these persons can generate their own anti-IFN antibodies.

Using cryopreserved blood plasma samples from these same persons receiving IFN-α or IFN-β treatment, respectively, the team isolated and cloned four selective anti-IFN antibodies, two against IFN-α and two against IFN-β. The researchers explained that the success of the novel approach taken—which leveraged the pooling of complementary DNA from original samples to optimize cloned antibodies—circumvents more complex techniques to derive monoclonal antibodies. Having demonstrated their antibodies’ ability to selectively block IFN-α or IFN-β in vitro, the team predicts that future studies in vivo will yield similar promising results.

“These novel, effective human antibodies against specific Type I interferons have the potential to be an indispensable tool for understanding and ultimately serving as immunotherapy against cancer, autoimmune or infectious disease conditions,” said Montaner.

“We are pleased with our methodological proof-of-concept report, and I believe it will lead to exciting future work,” added Papasavvas. “With the ability to selectively target and inhibit specific interferons, scientists will have a valuable tool for developing future therapies.”