WASHINGTON _ The recombinant DNA Advisory Committee(RAC) to the National Institutes of Health approved nine new protocolsat its two-day meeting last week, bringing the total number of protocolsapproved to 58.Two diseases new to the RAC were represented among the protocolsapprovals: rheumatoid arthritis (See BioWorld Today, June 10, 1994,p. 1.) and Fanconi's Anemia, an inherited disorder that can result inlow counts of red and white blood cells, and platelets, due to bonemarrow failure.The rest of the protocols covered cancer treatments.Three of the protocols considered on Friday involved use of cytokinesto prime the immune system against cancers. New interleukins (IL)have been discovered regularly, leading several members to wonderwhether it was worthwhile to keep testing each new one on humansubjects, and leading RAC member Gary Chase, department of mentalhygiene, The Johns Hopkins University to joke that so manyinterleukins "make dying more complicated." The difference in theiractivities was the underlying question.A particular advantage of IL-12 is that it acts very early during immuneresponse, said Michael T. Lotze, professor of surgery, moleculargenetics and biochemistry, and codirector of biologic therapy at thePittsburgh Cancer Institute. Lotze received approval, 10 to 0, with threeabstentions, to insert IL-12 subunit genes and a marker into patients'skin (fibroblast) cells, and then to inject the tranduced cells next to thetumor.Earlier in the day, one RAC member had said that cytokines mightwork better synergistically than separately. Lotze said that primatestudies suggested IL-12 might work best with IL-4, and that Hoffman-La Roche was planning to pursue this approach.Another cancer treatment using cytokines was approved in a record 10minutes, 13 to 0. Robert E. Sobol had proposed to inject irradiatedHLA-A2 matched tumor cells genetically modified to secrete IL-2 intoglioblastoma patients.But another trial, in which melanoma cells tranduced to secrete IL-7would have been used to vaccinate melanoma patients was deferred inlarge part because the researchers had not even started to collect animaldata on toxicity of IL-7."You have chosen to put us in a position to say we think it's safe to putIL-7 into humans," RAC member Robertson Parkman, head, thedivision of research immunology-bone marrow transplantation,Childrens Hospital of Los Angeles told the investigators. "There isn'tenough data for me to make an informed decision."The protocol was submitted by principal investigators James S.Economou, division of surgical oncology, John A. Glaspy, division ofhematology-Oncology, and William H. McBride, department ofradiation oncology, University of California, Los Angeles.Also on Friday, the RAC approved a protocol for injecting the p53tumor suppresser gene into lung cancer cells, while patients alsoreceive the chemotherapy drug cisplatin. The p53 gene is absent ormutant in many cancers, including cancer of the lung."It is a very bizarre, and possibly exciting observation," that cisplatinand the p53 gene product each can kill cancer cells, but that thecombination knocks them flat," said Robert Hazelkorn, professor ofmolecular genetics and cell biology at the University of Chicago.That protocol, from Jack Roth, department of thoracic andcardiovascular surgery at Texas Medical Center in Houston, also calledfor injection of both compounds into the pleural cavity, the spacebetween the lung and the body wall, a fluid filled area which may alsocontain free-floating lung cancer cells. This part of the proposal wasrejected, because animal testing had not been done, and RAC membersfeared that the retrovirus vector could prove toxic to the pleuralmembrane.Advisory Group Meets On Gene Therapy ProductionFollowing Thursday's RAC meeting, gene therapy pioneer FrenchAnderson of the University of Southern California convened an openmeeting on "Production Issues for Human Gene Therapy." The purpose was to set up mechanisms through which researchers canprovide the FDA with solid data on the safety of manufacturing and useof vectors, and other safety issues in gene therapy experiments. TheFDA can then alter the regulations where necessary to fit reality.Currently, FDA regulations are "very conservative," and based on goodguesswork rather than hard numbers, Anderson told BioWorld.Pressure had recently been building for change, because GeneticTherapies Inc., of Gaithersburg, Md., which has provided vectors freeof charge in the past, can no longer continue this largesse, andcompanies are preparing to supply their own."The FDA has been flooded with calls from companies asking if, "wehave to have a K-10,000 room," Anderson told BioWorld. Such roomscost in the hundreds of thousands of dollars to build. Unnecessarilyhigh safety standards could drive companies out of business, hewarned.Jeffrey M. Ostrove, senior vice president and chief scientific officer ofMagenta Corp., Rockville, Md., a company which performs safety-related contracting for biotech companies told BioWorld that thosetypes of buildings "require constraints such as seamless flooring andceiling, epoxy paint, and special air filtering capable of discriminatingparticles of less than 4 nanometers in diameter, and different airpressures."While companies should not have to buy more protection thannecessary, "one disaster will set the industry back a long way," Ostrovetold BioWorld. Several years ago in the UK, he said, smallpox fromone researcher's culture killed another researcher two floors down,because "the systems weren't in place to work with pathogens in acontrolled environment.""Replication competent viruses [vectors] do escape," said Ostrove."These are real events that occur in both preclinical and productionlots." In some cases, hard data might demonstrate the need for morestringent regulations. Whatever the case, "We will pool the data so thatit is anonymous for any company or person, and the FDA cancontinuously modify the rules to fit with experience," Anderson toldBioWorld.During the meeting, participants began to set up mechanisms for datagathering. They agreed to meet at the end of the first day of every RACmeeting. n
-- David Holzman Special To BioWorld Today
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