The recombinant DNA advisory committee (RAC) of theNational Institutes of Health (NIH) approved three moreprotocols Friday, two unanimously (as were the four itapproved Thursday)--on an interleukin-2 (IL-2) treatment formelanoma; and a treatment for HIV-1 infection with aribozyme that cleaves HIV-1 RNA.
But a third protocol, on autologous tumor vaccines producinginterleukin-1 (IL-1) for treatment of metastatic melanoma, wasapproved 11 to six abstentions, putting the lie to RAC memberAlex Capron's comment Thursday that the RAC was becominglike the Supreme Soviet.
Tapas DasGupta, head of the division of surgical oncology in theCollege of Medicine, University of Illinois at Chicago is theprincipal investigator for the pilot study of toxicity inimmunization of patients with unresectable melanoma with IL-2 secreting allogeneic human melanoma cells. And JamesEconomou of the University of California, Los Angeles is thelead investigator of the proposed trial on using geneticallyengineered autologous tumor vaccines producing IL-2 to treatmetastatic melanoma.
AIDS activist G'Dali Braverman of ACT-UP Golden Gate, who isHIV-positive, a regular at RAC meetings who has reviewedmany protocols himself, had high praise for University ofCalifornia, San Diego (UCSD), researcher Flossie Wong-Staal'sPhase I ribozyme protocol (see BioWorld, July 12). He toldBioWorld that he felt the general approach, of which thisprotocol is the first example, has considerable promise.
Briefly, Wong-Staal's protocol involves a retroviral vector thatcarries the gene for a catalytic ribozyme controlled by aspecific promoter that targets some of HIV's conserved RNA.The protocol calls for the retroviral vectors to be incubatedwith an HIV-infected patient's blood cells and then reinfusedinto that patient.
The University of California's technology transfer office islicensing the ribozyme technology to a company, which "islikely to be a San Diego firm," Wong-Staal told BioWorld. Sheimplied that the company had been chosen but would not nameit.
One requirement of the protocol which RAC members andBraverman considered ill-advised was the insistance by UCSD'sinstitutional review board (IRB) that patients be on AZT. "Ithink IRBs oversee and overlook," Braverman told BioWorld. Inits approval, the RAC waived that requirement, leaving thematter of AZT between patient and primary physician.
Braverman had other, more general suggestions forexperimental AIDS treatments. He advocated access tocompassionate use or follow-up protocols so that patients inPhase I trials would not lose later treatment options. Sinceresearchers on HIV treatments will be working in stem cells, hefelt that "it's critical that those (and CD4 and CD8) cells bestored," both for research purposes and for later treatments. Hesaid that "Storing those cells enables me to have access to themfor whatever therapeutics become available after my ownlevels fall below inclusion criteria for gene therapy trials."
This advice would apply to other types of studies as well,where such cells might be used for immune reconstitution.
On Thursday, the RAC had broached the possibility ofexempting certain types of studies from its approval process.Categories of vaccines and irradiated cells, and markingexperiments were chief among proposed exemptions. "Thoseactivities are not different from those already approved by theRAC," Steven Kradjian, director of regulatory affairs at SanDiego-based Vical Inc., told BioWorld. "They don't involvegreater subject risk, or different vector host systems, or anycompromises in quality control." Exemptions, he said, wouldspeed up research.
Five RAC members, including University of Illinois politicalscientist Ira Carmen, Robertson Parkman, head of the divisionof research immunology and bone marrow transplantation atChildrens Hospital of Los Angeles, Vice President ofexperimental therapy Leonard E. Post, of Parke-DavisPharmaceutical Division, and Doris T. Zallen, professor ofscience studies and humanities at VA Polytechnic Institute hadspent Thursday evening and Friday lunch mulling over theissues.
"The five of us were not going to reach consensus," Post toldBioWorld. And so the matter has been tabled at least untilDecember's RAC meeting.
"It may be up to six months or longer before anyimplementation of exemptions occurs," Kradjian lamented toBioWorld.
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.