NEW YORK _ "Opening up a whole new era of expression" ishow immunologist Nicholas Restifo described the cancer-vaccinehuman trial that is just beginning at the National Cancer Institute'sClinical Center.After it successfully prolonged survival of mice in his recombinantanti-cancer-vaccines group at NCI, the combination of tumorantigens and a co-stimulatory factor, interleukin-2 or the B7molecule, packaged in a cloned viral delivery vehicle, will get itsfirst test in patients, Restifo revealed here Tuesday at CancerVaccine 1994, an international gathering of cancer immunologistsand allied scientists.At the same session, Tuesday morning, immunologist MauriceGately of Hoffmann-La Roche Inc., of Nutley, N.J., divulged thatRoche "will be in the clinic by the end of this year" to study theanti-cancer efficacy of IL-12, another cytokine that has won itsspurs in mice, to treat patients with renal carcinoma.NCI's trial, Restifo told BioWorld Today, will enter patients withadvanced metastatic melanoma, whose tumor cells express theMAGE melanoma antigen, and whose immune systems arecompetent to fight the disease.The FDA, Restifo said, has already approved the use of vacciniavirus encoding these model tumor antigens, together with co-stimulatory adjuvant molecules, which heighten the antigenimmune response.That principle, which his group confirmed in mice, Restifo said, "isa critical new finding." Besides recombinant vaccinia, hisexperiments found fowlpox and adenoviruses equally efficaciousgene-delivery vectors."My group did these experiments," Restifo told his audience, by"American-style research." "That is," he explained, "we just trieddifferent cytokines, co-stimulatory molecules and restrictionelements. We don't theorize too much. Instead we try and see whatworks."Interleukin-12 also has potential as a vaccine adjuvant in the systemRestifo described, Roche's Gately told BioWorld. Althoughidentified several years ago, the cytokine has only now come to thefore of cancer immunotherapy, since successful mouse studies atthe Roche Research Center and, separately, by Genetics Institute(GI) of Cambridge, Mass. GI has already begun human trials, suchas Roche will soon undertake.Besides showing its worth in murine tumors, Gately added, "IL-12has very dramatic effects in various infectious-disease models,leishmaniasis, toxoplasmosis and so on." He observed that "inopportunistic infections such as HIV, cells from AIDS patients canrespond to IL-12."Cancer Vaccine 1994 winds up its three-symposium today, with anall-day agenda focused on "Strategies for the Development ofCancer Vaccines." Its sponsoring organization, the 43-year-oldCancer Research Institute, plans to repeat this year's internationalsymposium in future even-numbered years, said the institute'sdirector of communications, Brian Quinn. "We will continue thesebiennial events," he told BioWorld Today, "until the technology fordeveloping vaccines is down pat, and the vaccines themselves havebeen developed, and are in sufficient use _ at least, Phase III trials,let's say."In the odd-numbered years," Quinn added, "1995, `97 and so on,we'll be holding international symposiums on monoclonalantibodies, and their uses in analysis, diagnostics and eventuallytherapeutics for cancer patients." n

-- David Leff Science Editor

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