A Philadelphia biotech designed a first-of-its-kind therapy for rare cancer: Now, it waits for patients

Within the next couple of weeks, the first blood samples from patients will arrive at the loading dock of Adaptimmune, a biotechnology company headquartered on the northeastern edge of the Navy Yard.

Their arrival will open a new chapter in medicine’s ongoing search for a therapy that converts the body’s own immune system into a cancer-killing machine.

In August, the company’s signature therapy, Tecelra, became the first approved by the U.S. Food and Drug Administration that works by modifying a patient’s own immune cells to attack a solid tumor. Although the agency has okayed several other therapies that act in similar ways, previous treatments have been most successful in blood cancers, which represent only 10% of all cancers.

Tecelra’s approval for patients with synovial sarcoma, a rare form of cancer that strikes muscles and ligaments, represents a critical proof of concept: The engineered immune therapies that have revolutionized blood cancers can also work in solid tumors. It is also the first treatment advance in years for synovial sarcoma, a devastating cancer that is often diagnosed in people under the age of 30.

“It’s a movement of the field—and the science—forward,” said Natalia Rivera-Torres, a gene editing researcher at ChristianaCare in Delaware, who is not involved with Adaptimmune and the development of Tecelra.

Now, inside the halls of Adaptimmune—created in 2008 through a partnership with the University of Pennsylvania, an early pioneer in cell and gene therapy—the sense of anticipation is palpable.

A specialized assembly line

After arriving at the company’s loading dock, the first patient blood samples will travel via a dumbwaiter-like system to the second floor, then into the sterile processing rooms, where manufacturing specialists shift between stations wearing masks, gloves, goggles, and so-called bunny suits over their clothes and hair. (It can take up to 10 minutes to put everything on.)

In those sterile spaces, coated beads are added to the blood samples, designed to adhere to the patient’s specific immune cells used in Tecelra. Over the next couple of days, those extracted immune cells are mixed with a harmless virus that infects them with the genetic instructions they need to target the patient’s tumor.

The process takes time. The two rooms where the initial engineering takes place can each accommodate only four patients a week, estimated Mark Stielow, vice president of manufacturing and technical operations.

Once the patient’s immune cells have been programmed to become cancer-killers, they move to a room containing a series of white pods, each serving as an individual bioreactor. There, the cells sit for eight days with their favorite nutrients, temperature, and oxygen levels, rocking back and forth. And they multiply.

“We will start with, you know, in the neighborhood of about a billion cells or so when we load it up, and by the time we’re done, on day 12, we could have as many as 40 or 50 billion from each patient,” said Stielow.

But on a visit last month, the room was dark, quiet. The pods were still there. The first patient orders hadn’t yet arrived.

How it works

Tecelra has joined the ranks of immune therapies that modify a patient’s own immune cells to target markers on the surface of cancer cells. Collectively, these engineered immune therapies have revolutionized cancer treatment.

One such therapy, chimeric antigen receptor T-cell therapy, or CAR-T therapy, was also pioneered at the University of Pennsylvania, and has been heralded as a cure for some forms of blood cancer. The first child treated with CAR-T at Children’s Hospital of Philadelphia in 2012—a 6-year-old with terminal cancer—recently enrolled at Penn as an undergraduate student.

But CAR-T therapy has not worked well against solid tumors, which make up the vast majority of all cancers. The reason: Blood cancers have proteins on their cell surface that are good targets for engineered immune cells. Most solid tumors don’t.

Synovial sarcoma, however, does have a good target: a protein known as MAGE-A4.

Not all synovial sarcoma tumors carry MAGE-A4, and in the ones that do, the protein is present inside the cell. But fragments of MAGE-A4 end up on the cell surface, which allows therapies to target synovial sarcoma cells. Since MAGE-A4 is mostly absent from healthy cells, Tecelra will attack cancer cells but leave others alone.

Some other solid tumor cells can also carry MAGE-A4, including non-small-cell lung cancer, head and neck squamous cell carcinoma, as well as ovarian, melanoma, and gastroesophageal cancers.

Ideally, Tecelra will open the door to other immune therapies for these solid tumors, as well as others with different targets altogether. “If you can find the right target that you could build a [engineered immune cell] for, basically the options are limitless,” said Dennis Williams, the senior vice president for late-stage development at Adaptimmune.

A ‘major advance’

Getting Tecelra isn’t as easy as getting an oncologist to write a prescription. Patients have to undergo thorough testing to determine whether their tumors carry the precise markers targeted by the drug, and ensure their insurers will cover the costs. That’s key, given Tecelra’s roughly $700,000 price tag. (Some engineered therapies can cost millions of dollars for a single dose.)

Only 1,000 people have synovial sarcoma in the U.S., some of whom are now being screened at Adaptimmune’s authorized treatment centers for their eligibility to receive the drug.

Even though Adaptimmune hasn’t yet made any Tecelra as a treatment, the company has had plenty of practice designing hundreds of doses for use in research.

In a trial of 44 people with synovial sarcoma, roughly 40% responded to Tecelra. Two people had a “complete response,” meaning they showed no sign of the disease.

A 40% response rate may not sound impressive when compared to CAR-T therapy, which appears to cure some types of cancer after a single infusion. But Tecelra’s data are impressive, said Margaret von Mehren, chief of the division of sarcoma medical oncology at Fox Chase Cancer Center, who was not involved with Adaptimmune or Tecelra.

All of the patients had advanced forms of synovial sarcoma, and had failed at least one round of chemotherapy. In this population, if they were to try traditional chemotherapy, von Mehren said she wouldn’t expect more than a 20% response rate and a short time of disease control—maybe several months.

Tecelra is “a major advance,” she noted.

That said, Tecelra won’t work for all patients with synovial sarcoma. To receive the drug, patients’ tumors must express MAGE-A4, as well as the specific protein complexes recognized by Tecelra that bind MAGE-A4 fragments on the surface of cells.

“While it’s a step forward, it’s a step forward for a group of patients, not all patients,” von Mehren said.

Tecelra also only works for patients whose cancers are stable enough to wait out the time it takes to manufacture their engineered cells, said Teresa Lee, an assistant professor and practicing sarcoma physician at Fox Chase Cancer Center, who was also not involved in Adaptimmune and the development of Tecelra.

“It is not a process that will be appropriate or beneficial for every patient, but I hope that the oncology community will also become increasingly aware of this option, so that they can refer patients to centers offering it for treatment consideration and planning well ahead of time.”

Fox Chase is working to become an authorized treatment center for Tecelra, and von Mehren said she would recommend it if she had a patient who qualified to get the drug. “I think it provides a meaningful benefit.”

Some patients who took Tecelra in the earliest studies are even coming up on four or five years of no growth in their tumors—without using chemotherapy and radiation, said Adaptimmune’s Williams.

He compared the experience of getting Tecelra to the market to climbing a mountain range. “There’ve been a lot of peaks and hills to summit.”

And soon, patients will get the therapy the company worked so hard to create, Williams added. “This, at the moment, is the highest peak for me.”

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