While assigned to the Naval Medical ResearchCenter, Navy immunologist Dr. Carl Junemade a profound discovery—the key to ahypothesized second signal in T-cellstimulation. June’s discovery of the functionof the CD28 molecule in that second pathwayled to major advances in the search for safeand effective therapies for autoimmunedisorders. Academic and industrialcollaborations centering on this fundamentaldiscovery have resulted in the development ofrevolutionary new methods for treatingautoimmune diseases such as rheumatoidarthritis, lupus, multiple sclerosis, andscleroderma. These methods, using agenetically engineered form of a moleculenearly identical to CD28 (CTLA4-Ig), havebeen effectively transferred into the privatesector, as exemplified by U.S. Patent No.6,685,941, approved February 3, 2004. Thepatent is assigned to the Navy and theUniversity of Michigan and licensedexclusively to Repligen Corporation. CTLA4-based therapy for rheumatoid arthritis iscompleting the final phase of FDA-approvedtrials, with outstanding phase II results havingalready been reported.The Navy is listed on over a dozen otherrelated patents, which have been licensed andsublicensed to companies working in the fieldof ex vivo activation or expansion of humanT-cells for treatment and/or prevention ofAIDS, cancer and immunodeficiency states.Those companies include Repligen (whichworked under a CRADA with the Navy),Genetics Institute, Wyeth, and XcyteTherapies, a sublicensee created specifically tocarry out further research and development inthis area.Before the promising work with CTLA4-basedtherapies, treatment for autoimmune disordersrequired that the entire immune system besuppressed. Not only do these new methodspromise effective treatment of disease itself,they allow for continued immune function evenduring treatment.The work done under the auspices of the NavalMedical Research Center by Dr. June and hiscollaborators caused a sea change in theunderstanding and treatment of autoimmunedisorders, as evidenced by the recentlyapproved patent. The value and significance ofthe work cannot be overstated.