The first patient to receive a direct injection of a gene therapydrug for fighting AIDS was dosed Tuesday at the SharedMedical Research Foundation in Los Angeles. And on the EastCoast, the first patient to receive lymphokine gene therapy formalignant melanoma was injected Tuesday with autologouscells containing the gene for human gamma interferon at DukeUniversity Medical Center in Durham, N.C.
Both trials are being sponsored by privately held gene therapycompany Viagene Inc. of San Diego.
The protocol for the direct-vector HIV trial, which theRecombinant DNA Advisory Committee (RAC) of the NationalInstitutes of Health (NIH) approved June 8 (and for whichViagene received clearance from the FDA on Aug. 3), involves adirect intramuscular injection of a murine retroviral vectorencoding HIV-1 genes.
The patients targeted in this study are asymptomatic carriersof the deadly virus; the study is designed to ascertain whetherthe direct approach is able to prime patients' immune systems,specifically to stimulate a killer T-cell response. It uses thepatient as a unique factory to produce HIV-associated proteinsfor stimulating the individual's own cellular therapy.
Viagene has developed another sort of gene therapy protocol aswell, one that uses an ex vivo approach by which a patient'scells are removed via biopsy, cultured to expand theirnumbers, infected with a retroviral vector containing the geneof interest, and then inserted back into the patient.
Again, the theory is to stimulate the individual's cellularimmune responses. It is this protocol that Viagene has used todesign its trials on malignant melanoma, also approved by RACon June 8 and cleared by FDA on July 7. The vector inserts intothe patient's tumor cells the gene for human gamma interferon,which Viagene licensed non-exclusively for use in gene therapyfrom Genentech Inc. on July 8, according to Robert Abbott,Viagene's president and chief executive officer.
These modified and culture-expanded tumor cells are thenused in a series of 24 injections spread over a year as a tumorvaccine to enhance the patient's immune response against anymetastatic tumor cells.
The Phase I study, being conducted at Duke University byHilliard Siegler, is planned to eventually enroll 20 patients withmetastatic malignant melanoma for whom conventionaltherapies have failed. Right now, the goal is to "start at least ahalf-dozen patients on the protocol," said Abbott. Once a patienthas been biopsied, it takes about a month to prepare the cellsfor reinjection -- two weeks to culture the cells and anothertwo weeks for quality control. Cells from five patients currentlyare being cultured, Abbott added.
Viagene isn't the first company to test an immunotherapeuticapproach to treating cancer, said Abbott, but its approachdiffers.
"All the other protocols are designed to deliver to the site ofactivation of cytotoxic T lymphocytes (CTLs) the lymphokinesthat will stimulate the CTLs or NK (natural killer) cells toenhance the potency of the immune system. Viagene'sapproach is to enhance the recognizability of the tumor cells.We're working on the target side of the equation; the others areworking on the effector side of the equation," Abbott toldBioWorld. "These will probably be complementary therapies inthe end."
Viagene has also employed its ex vivo gene therapy approachto treat HIV infection, transfecting in vitro an infected patient'sfibroblasts with an HIV env gene in a retroviral expressionvector. In fact, four patients were accrued for those trials, andeach patient received a "full set of three injections," accordingto Abbott.
Those trials are complete; the company is conducting long-termfollow-up studies and is hoping to report preliminary biologicaldata before the end of the year at a scientific meeting, Abbottexplained. There are no plans to enroll more patients in the exvivo HIV gene therapy trials because "we had concluded afterdiscussions with the FDA that the direct vector study would beallowed to proceed," Abbott told BioWorld.
Viagene's partner, Green Cross Corp. of Osaka, Japan, hassupported the research, development and trials of both HIVimmunotherapeutics. The gene therapy company hopes by nextyear to "expand the indications for the gamma interferon genetherapy into other cancers or to extend the direct-therapy HIVtrials into the efficacy phase," Abbott said.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.