CAMBRIDGE, England -Start-up Lorantis Ltd. said it will treat allergic and autoimmune disease by returning the immune system to its normal state. It is commercializing research on Notch, an immune response modifier that occurs on the surface of T cells.

CEO Mark Bodmer told BioWorld International, "The big advantage we have over other approaches is that we have an antigen-specific system, which tolerizes to the offending antigen, rather than suppressing the immune system. Rather than compromising the immune system we will restore the normal tolerance most people have."

Notch was first described twenty years ago in Drosophila. Later, a mammalian equivalent was discovered on T cells. The question was, what was Notch doing on T cells? This now has been elucidated by the scientific founders of the company, Maggie Dallman at Imperial College in London, and Jonathan Lamb and Gerald Hoyne, both of the University of Edinburgh.

"The mechanism by which T cells launch an attack against bad foreigners such as flu is well described, but little is known about tolerance in molecular terms," Bodmer said. Such mechanisms govern how the immune system tolerates benign foreigners, for example, lunch, and how it tolerates self.

The research shows that if Notch is turned off the immune system switches to attack mode; if it is turned on the immune system tolerates the foreigner. "Notch is the molecular switch that says attack or tolerate; it is a very fundamental mechanism." Notch activation during antigen presentation results in T-cell tolerance that is antigen specific, long-lived, epitope-linked, disseminated and active and CD4 cell-mediated.

"These patented observations open up a wide range of new possibilities for specific immunotherapy without suppression of the immune system," Bodmer said. The technology will be applied to allergy, including hay fever and asthma; autoimmunity, including rheumatoid arthritis and multiple sclerosis; and transplantation, in both solid organs and cell replacement. The company has demonstrated Notch activation preventing an immune response in a mouse model of allergic asthma, and preventing rejection in a mouse model of transplantation.

Lorantis was established two years ago by the founding scientists with seed money from the venture capitalist Abingworth Ventures. The company is in the process of completing the first funding round of #3 million (US$4.5 million), which will finance it for 18 months. It has started recruiting staff, and head count will reach 20 by October.

Bodmer was formerly head of R&D at Incyte Genomics Inc. He assumed this post when Hexagen Ltd., of Cambridge, a mouse genomics company of which he was CEO, was taken over by Incyte 18 months ago. The chief scientific officer is Roberto Solari, formerly of Glaxo Wellcome plc.

With 18 months of funding Lorantis expects to complete discovery and have its first development candidates ready. It also will develop the technology as a platform, looking at related regulators on other pathways and finding new targets from conserved pathways that are defined in Drosophila and in the worm C. elegans.

Bodmer said he is not aware of any other companies working to commercialize Notch. "It is a big field in academic terms, but it was not until the founders worked out what Notch did in humans that its commercial possibilities were evident."