Seragen Inc.'s fusion toxin DAB486IL-2 kills HIV-infectedcells without harming healthy cells in test tube experiments.
But it will be some time before the drug is tested in humans, aSeragen representative told BioWorld. The privately heldcompany has just begun testing the drug's ability to targetinfected cells in HIV-infected immunodeficient SCID mice.
DAB486IL-2 consists of the toxic portion of diphtheria toxinjoined to interleukin-2. IL-2 targets the toxin to white bloodcells that have high-affinity IL-2 receptors on their surfaces.These receptors bind tightly to IL-2 and are found on diseasedand virally infected white blood cells.
Soon after HIV, the AIDS virus, infects T cell white bloodcells, the virus triggers the cells to express high-affinity IL-2receptors. This event occurs prior to viral replication,suggesting that DAB486IL-2 might block HIV infection at anearly stage.
Other targeted toxins, such as Upjohn Co.'s CD4-PE40 andRepligen Corp.'s CD4-ricin, are targeted to gp120, an HIVenvelope protein that is expressed on infected cells during thelate stages of viral replication. A bispecific antibody recentlydescribed by the University of California, San Francisco,Genentech Inc. and Chiron Corp. scientists also targets gp120.Oncogen's pokeweed immunotoxin, in contrast, targets the CD4receptor on T cells. HIV enters T cells when gp120 binds toCD4.
Seragen researcher Jean C. Nichols, Ph.D., and her colleaguesfrom the Harvard Medical School, the National Institute ofDental Research and Boston University of Medicine reportedlast week in Science that DAB486IL-2 seeks out and destroysHIV-infected T cells even when they are mixed together withhealthy cells in the test tube. The drug also delays healthy cellgrowth, but only for a short period of time.
Seragen, based in Hopkinton, Mass., is already conductingclinical trials of DAB486IL-2 as a treatment for severalleukemias and lymphomas, severe rheumatoid arthritis andinsulin-dependent diabetes.
These studies suggest the dose of DAB486IL-2 used to blockHIV infection is tolerated by patients and is notimmunosuppressive. However, since the immune system ofpatients with AIDS is severely compromised, animal studiessuch as those with the SCID mice are needed to ascertain howthe drug will affect the remaining healthy white blood cellsthat are fighting the HIV infection.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.