Enzo to begin trial of genetically modified stem cell-based HIV treatment

By Angela McDaniels

Seattle, March 1 - Enzo Therapeutics said it received approval from the Committee on Human Research at the University of California San Francisco to continue the clinical evaluation of the company's Stealth Vector HGTV43 gene construct for HIV-1 infection in a protocol that has been modified to increase the number of stem cells that engraft in the patient's bone marrow.

In the upcoming trial, Enzo's StealthVector HGTV43 gene construct will be used to transfer three antisense genes designed to interfere with the growth of HIV-1 into blood stem cells. These cells are expected to replicate and differentiate within the body of the HIV-1 infected individual to produce CD4+ T-cells, the main target of infection by HIV-1, according to a company news release.

Enzo said that the novel aspect of the current study is to increase the percentage of CD4+ cells that contain the anti-HIV-1 antisense genes with a protocol designed to partially reduce the patient's blood stem cells before infusion of the engineered cells.

The trial is intended to determine whether this procedure will create a supply of HIV-1 resistant CD4+ cells large enough to materially defer the disease progression of HIV-1 into AIDS in infected individuals.

A phase 1 study at the university demonstrated the safety of the procedure and showed that the engineered stem cells were able to survive long term in vivo and to produce a low number of CD4+ cell progeny containing functioning antisense genes, the company said.

Although there was no increase in the CD4+ cell count or reduction in the viral load, Enzo said the yield of engineered cells has remained more or less constant over a number of years, in the case of one individual for as long as five years, supporting the conclusion that stable engraftment of anti-HIV-1 antisense RNA-producing blood stem cells occurred and the antisense genes continued to function.

The regulatory approval process for the upcoming trial, which is expected to begin soon, included a comprehensive review of the clinical protocol and safety features of the vector by the research committee, the Food and Drug Administration and the Recombinant DNA Advisory Committee of the National Institutes of Health.

The company said the HGTV43 vector was developed to include its proprietary delivery system designed to overcome a major challenge in gene medicine, namely the efficient and safe delivery of the medicine to the appropriate target.

The benefits of Enzo's "Stealth" vector technology are that it achieves efficient delivery of the genes into the patient's cells and that it is silent and, therefore, unlikely to trigger an immune response, according to the release.

In addition, during the development of the vector, two critical safety features were incorporated to minimize the possibility of inadvertently turning on deleterious genes in the subject.

"Enzo has worked diligently, conducting extensive testing designed to assure the safety of our medicine, to reach this stage," executive vice president Dean L. Engelhardt said in the release.

"The sustained expression of our HGTV43 gene construct in circulating CD4+ T-cells strengthens our belief that this gene therapy protocol could function as a once-in-a lifetime treatment."

Enzo is a Farmingdale, N.Y.-based subsidiary of Enzo Biochem Inc., a biotechnology company based in Bridgewater, N.J., that researches, develops and manufactures health care products based on molecular biology and genetic engineering techniques.

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