Having its own facility will help Iovance intensify manufacturing of its tumor infiltrating lymphocyte (TIL) cell therapies and help to reduce the 22-day process, the firm says.

In May last year, Iovance Biotherapeutics announced plans to construct a 136,000 square-foot facility in Philadelphia, Pennsylvania for the clinical and commercial production of its autologous TIL products, including its lead candidate lifileucel in Phase II trials for metastatic melanoma.

Speaking last month at the Phacilitate conference in Miami, Florida, Michelle Simpson-Abelson, principle scientist at Iovance, said the having an internal network is one of the firm’s strategies aimed at reducing the cost of TIL production and increasing patient access.

Image: iStock/IvelinRadkov

The initial process was devised by Steven Rosenberg, chief of surgery at the National Cancer Institute (NCI), through 30 years of development, she said during a plenary fireside chat.

Initially it was a six-month manufacturing process, making the prospect of commercialization exceptionally difficult. “One of the first goals of Iovance was to come up with a process so that we could expand TIL in sufficient numbers to see clinical efficacy in a much shorter manufacturing process while cryopreserving the product.”

This led to a second generation 22-day process being developed involving the isolation of TIL cells from a patient’s own tumor and then the expansion of them by stimulating them ex vivo. At the beginning of the process, the cells are fragmented in a minimalized cell culture system for the first 11 days, before rapid expansion begins. On day 16 the cells are split into multiple flasks, and day 22 they are harvested.

“This is a fairly simplified process compared to the initial process that involved 24 well plates, and multiple plates and constantly splitting the cells,” said Simpson-Abelson.

“On average we’re able to expand TIL from a tumor biopsy to approximately 28 billion cells and still see fairly significant clinical efficacy.”

However, 22 days is still a long manufacturing turnaround for autologous medicine, moderator Anthony Davies, founder of cell and gene therapy specialist firm Dark Horse Consulting, pointed out.

“We are working on further optimization of our process to reduce the number of days without reducing the product’s efficacy,” Simpson-Abelson.

Currently Iovance uses third-party manufacturers to make lifileucel and its other TILs. One of the contract development and manufacturing organizations (CDMOs) used is Masthercell – set to be acquired by Catalent – which Iovance contracted in 2018 for the supply of late-stage clinical trial material in Europe.

But with a tech transfer to the Philadelphia plant in sight, Iovance is hoping to improve the process and reduce the cost. “The thought process of having our own manufacturing facility and being able to tweak the process is to allow it to be as accessible to as many patients as we can.”

According to Simpson-Abelson, Iovance hopes to submit a BLA for lifileucel in the third or fourth quarter this year. “We will hopefully begin shipping the drug in 2021, in line with our manufacturing facility [coming online].”