By David N. Leff
Editor's note: Science Scan is a round-up of recently published biotechnology-related research.
A trap baited with iron has caught and killed brain tumor cells in nine of 15 patients in a Phase I clinical trial.
The bait was a protein called transferrin, which ferries iron from its stores in the blood's hemoglobin to iron-using cells throughout the body. The killer was a recombinant, mutant human diphtheria toxin, fused with the transferrin to form a tumor-targeting search-and-destroy operation.
The targets were cancerous glioma cells in the brain, which require a lot of iron for their rapidly growing malignancy. The killing field was the NIH National Institute of Neurological Disorders and Stroke (NINDS); the executioner, neurosurgeon Edward Oldfield.
He and his associates infused their lethal conjugate directly into the brain tumors, by way of a special pressurized pump. They report their clinical results in the December issue of Nature Medicine, under the title: "Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors."
Two of the 15 subjects experienced complete regression of their glioblastoma tumors; seven others, tumor shrinkage of 50 percent or better. All of the participants had exhausted conventional surgical, radiation and chemotherapy treatments.
Of the 17,000 brain cancers diagnosed each year in the U.S., the most common, and rapidly lethal, is glioblastoma, which is why the co-authors chose it to test their new antitumor fusion protein and pump.
This malignancy is the third leading cause of cancer death in persons 15 to 34 years of age.
European Immunologists Successfully Test Previously Disappointing Disease Bacterial Antigen, OspC, As Curative Vaccine In Mice
Before 1975, no one had ever heard of Lyme disease, since named for the picturesque Connecticut village where, in that year, its first outbreak occurred.
Now, the tick-borne, corkscrew-shaped (spirochetal) bacterium, Borrelia bergdorferi, infests 47 of the 48 contiguous United States, and has spread to a score of countries in Europe, Africa, Asia and Australia.
Immunologists on both sides of the Atlantic are struggling to produce vaccines that will both prevent and cure the debilitating infection. When they discovered OspA, an antigenic protein on the outer surface of the B. bergdorferi spirochete, they thought they were on to something. They were, but it wasn't everything.
OspA, it turned out, decorates the bacterial surface when the tick injects it into its victim's skin. But there, when the blood meal begins, the spirochete divides and begins expressing OspC, a quite different protein. (See BioWorld Today, April 23, 1997, p. 1.)
In clinical trials, OspA made a pretty good protective vaccine, but fared poorly at therapeutic treatment of the established infection.
Now a German-Swiss team of researchers has checked out OspC in mice. Their paper in a recent issue of the Proceedings of the National Academy of Sciences (PNAS), dated Nov. 11, 1997, is titled: "Therapeutic passive vaccination against chronic Lyme disease in mice."
"Our initial finding," they report, "that the presence of high serum titers of anti-OspC antibodies correlates with spontaneous resolution of disease and infection in experimentally challenged immunocompetent mice suggested that therapeutic vaccine with OspC may be feasible."
Their OspC vaccine completely cleared the chronic arthritic and cardiac pathologies of the disease, at whatever stage in the infection they flared up. "Thus," the co-authors conclude, "an OspC-based vaccine appears to be a candidate for therapy of Lyme disease."
NCI's Laser Capture Microdissection
Technique Extracts Individual Cells
From Surrounding Tissue Integument
Plucking a single cell of interest from a surrounding neighborhood of tissue can be a messy business. Scientists at the National Cancer Institute (NCI) have developed a better way, and licensed it under a CRADA (Cooperative Research and Development Agreement) to Arcturus Engineering, of Mountain. View, Calif.
"[T]he task of analyzing critical gene expression patterns in development, normal function and disease progression depends on the extraction of specific cells from their complex tissue milieu." So wrote molecular oncologist Lance Liotta in a recent issue of Science, dated Nov. 21, 1997. The article of which he is senior author bears the title: "Laser capture microdissection [LCM]: Molecular analysis of tissue."
Here's how LCM works:
First, cover the microscope slide holding the tissue sample with an ultrafine thermoplastic polymer film. Then focally bond this film to the slide.
Next, through the microscope, locate the cell of interest, and zap it with a laser pulse activated by the 'scope's optics.
"At this precise location," the Science paper explains, "the film melts and fuses with the underlying cells of choice. When the film is removed, the chosen cells remain bound to its undersurface, while the rest of the tissue remains behind." The brief meltdown's heat, they point out, does not damage DNA, RNA or proteins. And precision of transfer "can approach one micron."
"With LCM," the paper states, "the procurement of specific cells from a complex tissue section is reduced to a routine method amenable to widespread research and clinical diagnostic use."
Liotta heads NCI's Tumor Invasion and Metastasis Section. The institute's Cancer Genome Anatomy Program is now using LCM "to catalogue genes expressed in human tissue, as normal cells undergo premalignant changes en route to invasive and metastatic cancer." *