Xoma Corp. announced last week that it has reached a cross-licensing agreement with the University of Texas M.D.Anderson Cancer Center on technologies for recombinant DNA-derived gelonin (r-gelonin). Financial terms were not disclosed.
Gelonin, an enzyme that is derived from plant seeds, is anatural toxin that inactivates ribosomes.
Under the terms of the agreement, Xoma (NASDAQ:XOMA) hasexclusive worldwide rights to the r-gelonin technologies forcertain applications in autoimmune diseases and non-exclusiverights for other applications. The technologies, which weredeveloped by Xoma scientists together with researchers at M.D.Anderson led by Michael Rosenblum, may be sublicensed.
Xoma researchers have incorporated recombinant gelonin intoa targeted immunofusion (TIF) protein directed against CD5, anantigen on mature T lymphocytes, which are involved inautoimmune diseases such as rheumatoid arthritis. The goal isfor the TIFs to specifically bind to cells that express the targetantigen and then eliminate them by inhibiting proteinsynthesis.
Speaking at the Fourth International Conference on AntibodyEngineering in San Diego earlier this month, Marc Better,Xoma's director of molecular genetics, presented datademonstrating that a bacterially expressed CD5-r-gelonin TIFpotently and specifically eliminates CD5-bearing cells.
Better also described how company researchers have been ableto genetically fuse the plant-derived gelonin gene withhumanized murine single-chain antibody fragments (theantigen-binding domain) and then express it in the bacteriumEscherichia coli as a single protein. The bacteria secrete thefusion protein in a "fully folded and functional form" at about500 milligrams per liter, explained Stephen Carroll, Xoma'sdirector of biological chemistry.
"This is the first time that anyone has linked the components ofan immunotoxin genetically," Carroll told BioWorld.
As well, researchers at Xoma of Berkeley, Calif., selected thecomponents in the fusion molecules for their potency andreduced toxicity and immunogenicity. "We've engineered themto be as human-like as possible," Carroll said.
Xoma plans to enter a product based on TIF technology intoclinical testing in 1994.
-- Jennifer Van Brunt Senior Editor
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