A small biotech company is poised to shake up the world of oncology next year by launching the first personalized T-cell therapy for a solid tumor cancer. Until now, the technology has succeeded only in certain blood cancers.

Making the leap to solid tumors would be huge for cancer patients, as well as Philadelphia. Iovance Biotherapeutics this summer broke ground for a $125 million, 136,000-square-foot facility at South Philadelphia’s Navy Yard complex that will produce the T-cell therapy, called lifileucel.

“We are terribly excited with things that are happening,” said Maria Fardis, CEO of Iovance, based in San Carlos, Calif. “We hope to be the first cell therapy to be approved for a solid tumor cancer.”

Maria Fardis, CEO of Iovance Biotherapeutics
Iovance Biotherapeutics
Maria Fardis, CEO of Iovance Biotherapeutics

Treatment built on T cells, the soldiers of the disease-fighting immune system, has already transformed the prognosis for patients with certain advanced blood cancers. Two such “CAR-T” therapies have been approved by the U.S. Food and Drug Administration. The first, Novartis’ Kymriah, was developed at the University of Pennsylvania and Children’s Hospital of Philadelphia.

But the CAR-T approach — which involves genetically engineering each patient’s T cells to recognize and kill malignant blood cells — simply hasn’t worked well in solid tumors, despite vast research efforts. And solid cancers make up 90% of the 1.7 million new cancers diagnosed annually in the United States.

Instead of modifying T cells, Iovance extracts a rare subset that has the natural ability to zero in on the abnormalities that distinguish tumor cells. These elite “tumor-infiltrating lymphocytes,” or TILs, are normally suppressed and outmaneuvered by fast-mutating cancer. Iovance isolates TILs from the patient’s tumor biopsy, multiplies them by the billions in the lab, then returns them to the patient to launch a sustained attack.

TILs overcome a big obstacle to cell therapy: finding markers, or antigens, to target on cancer cells. CAR-Ts are rigged to go after only one antigen, and they can have lethal “off-target” effects, killing healthy cells that were not known to carry the antigen. TILs, in contrast, recognize the exquisitely complex array of antigens that are unique to the patient’s tumor cells.

Iovance licensed TIL technology from the lab of the scientist who pioneered it more than 30 years ago: Steven A. Rosenberg, chief of surgery at the National Cancer Institute. Melanoma patients were the first to experience dramatic remissions.

Steven A Rosenberg's lab at the National Cancer Institute pioneered technology for finding elite T cells that can attack solid tumors
National Cancer Institute
Steven A Rosenberg's lab at the National Cancer Institute pioneered technology for finding elite T cells that can attack solid tumors

Now, Iovance appears to be on the cusp of winning FDA approval of TILs for advanced cervical cancer and metastatic melanoma. The agency has agreed to let the company expand ongoing clinical trials and use the results to seek approvals in the second half of 2020.

The results so far, presented by Iovance at a conference in June, are striking.

Of 27 women with advanced cervical cancer that had defied available therapies, 12 (44%) saw their tumors shrink with lifileucel, including one whose disease disappeared. Many responses were sustained; after a median follow up of seven months, 10 women had no tumor progression.

Of 66 melanoma patients, 25 (38%) responded, including two who had no evidence of disease. After a median follow up of nearly nine months, 17 had no tumor progression.

Iovance also has trials in head and neck cancer and lung cancer. The company is partnering with academic medical centers to test TILs in ovarian, pancreatic and bladder cancers, and sarcomas.

Like CAR-Ts, TILs have substantial toxicity.

In Iovance’s melanoma trial, for example, almost all patients had severe or life-threatening side effects, and one patient died of a complication possibly related to the therapy.

But also like CAR-Ts, TILs offer the chance for a cure with a one-and-done treatment — even in deathly ill patients who have exhausted standard options.

“We’re out beyond 10 years in some cases, so very likely it is a curative treatment for patients with metastatic melanoma,” Rosenberg told the ASCO Post, an oncology publication.

Penn immunotherapy researcher Carl June, whose lab invented Kymriah, was duly impressed three years ago when Rosenberg’s team reported using TILs to eradicate metastatic lung tumors driven by mutations so invulnerable that they were considered “undruggable.” June wondered, however, whether the feat could be repeated.

Penn's Carl June believes tumor-infiltrating lymphocytes, or TILs, could be effective against a number of solid tumor malignancies.
ANDREW RENNEISEN / File Photograph
Penn's Carl June believes tumor-infiltrating lymphocytes, or TILs, could be effective against a number of solid tumor malignancies.

Now, he sounds bullish.

“Recent advances in the understanding of cancer and the immune system have made a compelling case that TIL therapy could be effective in diverse cancers beyond melanoma, such as lung cancer and cervical cancer,” he said by email. “The decision of Iovance to conduct commercial scale manufacturing in the Philadelphia Navy Yard is wonderful news.”

Iovance has figured out how to make TIL therapy in 22 days, compared with 42 days at Rosenberg’s NCI lab. The company has contracted to use another Navy Yard drug manufacturing facility until its own plant is up and running in 2021.

“Iovance’s investment in our city is further proof that Philadelphia is the epicenter for cell and gene therapy research and manufacturing,” Mayor Jim Kenney said in an email.

Fardis, an organic chemist and former Gilead Sciences executive who became Iovance’s CEO in June 2016, gets credit for turning the firm around. In 2014, when Iovance was called Lion Biotechnologies, then-CEO Manish Singh resigned amid a stock promotion scandal. Under Fardis, Iovance has not only made progress toward a scientific breakthrough, but also impressed Wall Street analysts. The company has no debt, lots of cash, and is valued at $1.2 billion, sixfold more than when Fardis took charge.

One looming challenge is the price of custom-made immunotherapies. Last month, Medicare finalized its long overdue decision on how to reimburse for Kymriah and competitor Yescarta, both approved in 2017. These CAR-Ts cost $375,000 to $475,000, and intensive hospital care can push the total to $1 million or more. The agency struggled to find a sustainable payment structure, but the plan is already being decried as “insufficient,” according to the Washington Post.

Fardis said lifileucel’s pricetag hasn’t been set yet, but the cost of production can be considerably less than that of CAR-Ts.

She predicted that over the next 10 to 15 years, as more cellular immunotherapies come on the market and reshape cancer care, the price will come down.

“I’m optimistic that we can do things over time to make it more acceptable,” she said.