BETHESDA, Md. _ The Recombinant DNA Advisory Committee(RAC) of the National Institutes of Health (NIH) approved studies offive new gene therapy products on Monday and Tuesday, includingexperimental treatments for metastatic melanoma, chronicgranulomatous disease, glioblastomas and ovarian cancer.
Targeted Genetics Corp. won clearance from RAC to conduct aPhase I trial testing the safety and immunologic effects ofadministering Interleukin-7 (IL-7) producing melanoma cells as a"vaccine" to patients with metastatic melanoma.
If approved by the FDA, the open label 25-patient trial will be thefirst time that IL-7 has been administered to humans. RAC deferredapproval of the trial protocol when it was first submitted at a meetinglast June, due to concerns about inadequate toxicological and safetytesting in animals.
Seattle-based Targeted Genetics is currently conducting additionaltoxicology studies on the IL-7 vaccine that were requested by theFDA after its review of an investigational new drug application(IND) filed late last year. Although the NIH's RAC still reviews mostgene therapy protocols, the FDA controls the clinical trial process forall new therapeutics under its IND program. Efforts to streamline andeliminate these overlapping responsibilities are currently under way.
In the experimental IL-7 trial, tumor cells will be removed frompatients and mixed with melanoma cells that have been geneticallymodified with Targeted Genetics' IL-7/HyTK retroviral vector tosecrete IL-7. The IL-7 producing cells will be treated with radiationto prevent their possible replication, and will be injected back intothe patient. The trial will tests three different "doses" of this therapy.
While some of the patients in the trial will receive their owngenetically modified tumor cells, some will be receiving cells from aformer melanoma patient whose cell line, labeled M-24, is owned byUniversity of California, Los Angeles (UCLA). Thus, the protocolseeks to evaluate the effects of both autologous (derived from thesame individual) and allogeneic (derived from a same-species,genetically different individual) IL-7-producing melanoma cells inmetastatic melanoma patients.
Although dubbed a vaccine, the IL-7 melanoma treatment is intendedto augment a patient's immune response to malignant melanomatumors, not to make the patient immune to other cancers or to preventcancer in the future. According to Targeted Genetics, animal modelshave shown that tumor cells genetically modified to produce IL-7 canstimulate an effective immune response against tumors.
The IL-7 melanoma vaccine trial is a collaboration between scientistsat Targeted Genetics and the UCLA. Principal investigators includesJames Economou, professor of surgery, William McBride, professorof radiation oncology, and John Glaspy, associate professor ofmedicine.
RAC approved four other research protocols during a two-daymeeting. Those included:
* A protocol to test an experimental gene therapy treatment forchronic granulomatous disease. The study will be led by HarryMalech, a researcher at the NIH's National Institute of Allergy andInfectious Diseases (NIAID), and conducted with the activecollaboration of Somatix Therapy Corp. and Baxter Healthcare Corp.Somatix, of Alameda, Calif., is providing a replication defectiveretrovirus vector for the trial.
* A Phase I trial of in vivo gene therapy with the herpes simplexthymidine kinase/ganciclovir system for the treatment of refractory orrecurrent ovarian cancer. Charles Link and Donald Moorman,researchers at the Human Gene Therapy Research Institute, in DesMoines, Iowa, will serve as principal investigators of the trial.
* A Phase I/II study of a new therapeutic approach to prostate cancerwherein vectors containing two cytokine genes simultaneously(Interleukin-2 and gamma interferon) are introduced into tumor cellsto generate specific host-antitumor killer cells. Bernard Gansbacher,a researcher at Memorial Sloan-Kettering Cancer Center in NewYork, is the principal investigator.
* A Phase I/II pilot study to evaluate the safety, relative survival andpotential efficacy of infusions of activated, genetically engineered,syngeneic CD4 cells obtained from HIV seronegative identical twins.The ability of these infused cells to boost the immune system of theHIV-infected identical twins will be measured. The protocol is beingsponsored by researchers at the NIH's National Center for HumanGenome Research in Bethesda and the principal investigator isRichard Morgan. Paul Tolstoshev of Gaithersburg, Md.-basedGenetic Therapy Inc. is listed as a collaborator on the study. n
-- Lisa Piercey Washington Editor
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