Gene and cell therapy developer American Gene Technologies International’s (AGT) lead candidate is its genetically modified autologous T-cell product AGT103-T, intended to be an HIV functional cure. Last month, the firm announced completion of pilot runs resulting in a product it believes is nearly four times the level necessary to restore HIV immunity in HIV-positive individuals.
According to AGT’s CEO Jeff Galvin, the product “is the most complex cell therapy the industry has delivered to date,” so we spoke with the firm to understand how it completed process development for AGT103-T’s automated cell manufacturing protocol, and how it will look to increase production as it progresses through clinical trials.
12 day process
Enriched leukapheresis product collected from normal peripheral blood – or a leukopak – is taken from study participants who are HIV positive, and then sent to AGT’s cell process development partner Miltenyi Biotec in Sunnyvale, California, David Pauza, AGT’s chief scientific officer, told Biopharma-Reporter.
“A single leukopak allows one pilot run for cell process development, working at the scale required to support a clinical trial,” he told us.
There follows five steps: 1) The purification and culturing of peripheral blood mononuclear cells (PBMC) from the leukopac using Miltenyi Biotec’s semi-automated CliniMACS Prodigy machine; 2) The stimulation of PBMC with synthetic peptides representing the HIV Gag polyprotein; 3) Transduction with the lentivirus vector AGT103; 4) Cell growth using the Wilson Wolf Manufacturing’s G-REX culture system; 5) Cell harvesting using the CliniMACS Prodigy machine with automated washing and cryopreservation.
“The process requires 12 days starting with receipt of the leukopak at Miltenyi’s processing,” Pauza said, adding it is “optimised for efficient use of the cGMP lentivirus vector stock and produces a single, cryopreserved, autologous cell dose for infusion.”
The process was developed at AGT laboratories in Rockville, Maryland and the firm is now preparing for a Phase I clinical trial this summer involving 18 patients.
And while its contract manufacturing organisation (CMO) Miltenyi Biotec has capacity and expertise necessary to support this, Pauza said the firm will evaluate its manufacturing strategies “including whether to pursue central laboratory or distributed cell processing” as the candidate moves through the development process.
“Miltenyi’s platform is appropriate for a variety of strategies including scaling up cell processing to accommodate clinical trials. Growth and new product development in the cell processing area is expanding the options for commercialization strategies and providing many choices for companies like AGT.”