COLD SPRING HARBOR, N.Y. G- Viagene Inc. of San Diego willlaunch a Phase I clinical trial of its proprietary AIDSimmunotherapeutic before the end of this year, according toDouglas J. Jolly, the company's research director.
He made the announcement at a recent international GeneTherapy meeting here.
The strategy "turns peoples' own cells into little vaccinefactories," he added.
A Los Angeles clinic has begun punching out small cylinders ofskin (3mm. in diameter) from the arms of individuals infectedwith HIV who do not yet show any symptoms of AIDS andwhose CD4 counts top 500.
So far, said Steven J. Mento, Viagene's vice president of R&D,"four or five people of the 12 planned for the trial have beenskin-biopsied to supply fibroblast cells for the custom-tailoredvaccine product."
In vitro, these cells are transfected with an HIV env gene,which encodes the entire envelope protein of the virus in aretroviral expression vector constructed by the company.
"This rationale," Jolly said at the conference, "is one stepbeyond treatment with (subunit peptide fragments such as) gp160." During two to four months of incubation, cell density willinitially reach 10 million per ml. The amplified transgenicfibroblasts then will be re-injected into the human testsubjects, for a two-pronged intracellular immune assault ontheir HIV infection:
-- The antigenic proteins are expected to trigger cytotoxic Tlymphocytes G- killer cells G- that destroy cells infected withthe AIDS virus.
-- Simultaneously, the fibroblasts will express the HIV envgene's envelope protein in several bits and pieces. Thesediverse fragments act as antigens that specific antibodydefenses attack selectively, varying from one individual toanother.
Half of the dozen patients in the trial will be inoculated withthe transduced fibroblasts, which are irradiated just beforereimplantation to prevent them from replicating. The other halfwill receive placebo fibroblasts that lack the HIV env gene.
If and after the Phase I trial proves Viagene's approach safe,these control patients will be offered a cross-over chance toreceive the active version of the cells, Mento told BioWorld. ThePhase I study is expected to take one year, but follow-up on alltrial subjects will continue for three years.
In June, the FDA's Vaccine Advisory Committee approvedViagene's plan, and the company filed an investigational newdrug (IND) application, which permits it to proceed with thePhase I study. Viagene will present its protocol informally tothe NIH Recombinant-DNA Advisory Committee at RAC's nextmeeting, Dec. 3 and 4.
But since Viagene does not receive any NIH funding, thecompany does not require its permission to proceed.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.