WASHINGTON -- The Recombinant DNA Advisory Committee(RAC) of the National Institutes of Health on Friday approvedtwo Phase I/II trials sponsored by Vical Inc. that use the SanDiego company's gene therapy product, Allovectin-7.

The first trial, in patients with renal cell carcinoma, will beconducted at the University of Chicago Medical Center underthe supervision of principal investigator Nicholas Vogelzang.Another trial testing Allovectin-7 in patients with malignantmelanoma will be carried out by Evan Hersh at the ArizonaCancer Center in Tucson.

These two approved Allovectin-7 protocols, as well as oneapproved by RAC last December using the same agent inpatients with metastatic colorectal cancer, are covered underan investigational new drug application (IND) filed by Vical inJanuary and approved by the FDA in February.

According to Vical's vice president for business development,Robert Zaugg, Allovectin-7 has been successful at stimulatingan immune response to tumors in mice. The product is a naked,double-stranded DNA plasmid, approximately 5,000 base pairslong that is mixed with a lipid material proprietary to Vical.The DNA plasmid-lipid mixture is injected directly into thetumor mass.

Once incorporated into the nuclei of cancer cells in the patient,Allovectin-7 will theoretically cause the transfected cells toproduce major histocompatibility complex (MHC) molecules,crucial elements of the immune system. MHC molecules alertimmune system killer cells to the presence of foreign orabnormal material on cells in the body and induce them todestroy those cells.

According to Zaugg, Allovectin-7 encodes for the production ofMHC that is antigenically mismatched from that of the host.Unlike retroviral vectors, Allovectin-7 is not incorporated intothe patient's genome but rather remains episomal, a free-standing circle of DNA that is still able to participate in thetranscriptional and translational activities of the cell.

Zaugg said that in animal studies, once even a small percentageof tumor cells are revealed to the immune system -- via theirunmasking by the boost in MHC production -- the natural"killer" T cells will seek out and destroy even non-transfectedtumor cells.

Allovectin-7 is the flagship product for Vical, one of the fewcompanies able to complete two public offerings in 1993 -- aninitial public offering in March for $12 million and a follow-onoffering in July for $16 million. "It's our first product, our mostvisible and the one that gets the lion's share of our resources,"Zaugg told BioWorld. However, an interleukin-2-expressingplasmid is currently under study, and Vical may file an IND forthat compound by the end of 1994.

Like monoclonal antibodies, transcription technology andantisense before it, gene therapy is now the darling of themedia and Wall Street. Zaugg concedes that it remains to beseen if this technology actually works. "We're aware that areasthat are hyped often fail to meet the high expectations even ifthey do succeed," said Zaugg.

He added that immune therapy for cancer has worked inanimal models for years but did not prove efficacious inhumans. Thus, even with promising animal data, there is noguarantee of efficacy for companies developing gene therapydrugs. "The field will wax and wane with product success," hesaid.

Vical's stock was up 25 cents a share on Friday, closing at $12.

-- Lisa Piercey Washington Editor

(c) 1997 American Health Consultants. All rights reserved.