By Jennifer Van Brunt
Baxter International's Biotech Group announced Tuesday that it has formed a genetherapy business unit to consolidate its research and development efforts for creating newtherapies to treat cancer, hemophilia and diabetes.
Baxter's gene therapy efforts are currently being conducted at the company's researchfacilities in Round Lake, Ill., and Santa Ana, Calif. As well, the multinational company(NYSE:BAX), headquartered in Deerfield, Ill., has an ongoing relationship with theWeizmann Institute of Science in Israel.
Baxter's major programs are focused on gene therapies for treating hemophilia andcancer, explained William Johnston, who heads the new gene therapy business unit.
“In both these areas, we anticipate that we will initiate a humanproof-of-principle clinical trial by the end of next year,“ with both protocols beingsubmitted to the Recombinant DNA Advisory Committee (RAC) of the National Institutes ofHealth (NIH) by mid-1994, he said.
Baxter has a long history of involvement in developing products to treat hemophilia.The company funded the research conducted at Genetics Institute Inc. (NASDAQ:GENIZ) thatled to the isolation and characterization of the gene for the blood-clotting proteinFactor VIII. That collaboration spawned Recombinate Antihemophilic Factor, a bioengineeredFactor VIII protein that FDA approved in December 1992 for treating hemophilia A.
Two months later, FDA approved another version of recombinant Factor VIII for treatinghemophilia A. That product, termed Kogenate, was developed by Miles Inc. in partnershipwith Genentech Inc., which cloned the gene.
Some outstanding ownership issues remain concerning recombinant Factor VIII, but Baxterhas a direct license from Genetics Institute as well as cross licenses. “ThroughBaxter's long-standing interaction with Genetics Institute and its own hemophiliabusiness, the company has secured the rights to the full-length Factor VIII,“Johnston told BioWorld.
Two Approaches for Hemophilia
Baxter scientists are now developing two separate types of gene therapy for treatinghemophilia. In a relatively standard approach, the researchers are engineering human cellsto produce Factor VIII; those cells then would be transplanted into patients.“Effectively, patients will function as though they are cured,“ Johnston said.“They will still have hemophilia, but they will have a continuous in-body mechanismfor producing Factor VIII.“
In a more novel approach to gene therapy for hemophilia, Baxter researchers aredevising a way to isolate and contain genetically engineered material in a membrane“sack“ implanted in the patient's body. This sack would shield the implantedtissue from the host's immune system while allowing the Factor VIII protein to diffuseinto the bloodstream.
“This gives us the ability to look at allogeneic gene therapy, with the addedadvantage of not having to use immunosuppressive drugs,“ Johnston told BioWorld.The method would have a “tremendous impact on the cost of providing thetherapy,“ he added.
Baxter scientists have explored this novel gene therapy system in animal models --mice, rats, pigs and dogs -- and have presented data at a number of symposia this year,including a presentation by researcher Jim Brauker at a recent Gordon Conference onBiomaterials, Johnston said. The results are also in press at this time.
“As a mechanism of facilitating gene therapy, we think this is going to be one ofour core fundamental technologies,“ added Johnston.
Gene Therapy for Cancer
In cancer, Baxter is developing a gene therapy approach based on technology developedat the Weizmann Institute by Zelig Eshhar. This approach involves splicing theantigen-recognition region of a monoclonal antibody into the receptor for T cells. Theengineered cell, called a T-body, may be able to target and destroy tumor cells.
“We've linked the T-body technology with Baxter's cell selection and cellseparation technologies,“ Johnston explained.
Baxter intends to seek “beneficial partnership relationships“ for itsdeveloping technologies and “in turn, we need to integrate technological advancesthat others can offer us into a larger gene therapy picture,“ said Timothy Anderson,president of Baxter's Biotech group. “The business may then emerge as a web ofinterlocking relationships among licensees, partners and joint ventures.“
Baxter already has options on a variety of cell lines, antibodies and other necessarycomponents for its gene therapy program, added Johnston, and is interacting withresearchers at the City of Hope and Michigan State University.
“We are in the process of looking at collaborations with other gene therapycompanies, where we would access vector technologies to supplement the technologies beingdeveloped at Baxter,“ Johnston added.