TIL Therapy Shows Promise in Non-Small Cell Lung Cancer
Deborah Barker feels most at home in the water. She could swim before she could walk growing up in Florida. She became scuba certified as a teen, and as an adult, she has traveled the world — the Galápagos Islands, Cuba, Belize, the Philippines and the Red Sea to name a few — diving and taking underwater photographs.
Deborah Barker has been around the world of scuba diving over the past few decades.
“I Zen out when I am underwater,” said Barker. “I have a reputation when I go on trips. The guys who fill our tanks always say I use the least amount of air so I am very comfortable. It’s very peaceful for me.”
But in the fall of 2017, Barker lost that peace. She noticed a weird back pain, and thinking it was related to a previous injury, requested an MRI. The scan showed a concerning lesion near her spine, and a biopsy revealed Barker had stage 4 non-small cell lung cancer (NSCLC).
Barker was anxious to start treatment immediately. Her wetsuit and dive equipment were stored, the possibility of another trip hanging in limbo.
“I wasn’t sure if I was even going to be alive.”
Finding New Options
While shocked to hear about her own diagnosis, Barker was familiar with cancer. The women in her family have a history of breast cancer and her father died from lung cancer in 2000.
“I went through it with him. From diagnosis to death it was about six months and I watched him feel miserable in treatment to only get about an extra month of life,” said Barker. Because of that experience and the advanced stage of her own cancer, Barker did not want to undergo the standard treatment regimen of chemotherapy.
According to the National Cancer Institute, NSCLC makes up about 80% to 85% of lung cancers. While it is the most common form of lung cancer, current treatment options do not cure the disease for most patients. There is only about a 25% five-year survival rate for NSCLC.
Barker started radiation for the tumor on her spine, but genetic testing of her cancer showed no mutations that could be treated with newer targeted medications. So, she began looking for a clinical trial.
“My sister went through a clinical trial for acute aplastic anemia and I was her stem cell donor in 2006,” said Barker. “I was very impressed with it all and was biting at the bit to get on a trial myself.”
After being disqualified at the last minute for a trial because doctors couldn’t get a big enough biopsy of her tumor, Barker came to Moffitt Cancer Center in February 2018. There, she found hope in a new clinical trial for tumor-infiltrating lymphocyte (TIL) therapy, a type of cellular immunotherapy that has shown success in melanoma and was being newly tested in patients with NSCLC. It extracts immune cells present inside tumors, grows billions of them in a lab and then infuses them back into the patient to attack the cancer.
Barker found hope in a new trial, led by thoracic oncologist Dr. Ben Creelan.
T cells are a type of white blood cell that helps the immune system fight off infections. They can recognize cancer cells as abnormal and work to kill them, however, sometimes the tumor can weaken the immune system so much it prevents T cells from doing their job. Checkpoint inhibitor drugs were developed to release the brakes cancer can put on T cells and allow them to attack tumors.
“We have had a lot of great milestones for stage 4 NSCLC, but most of the new treatments, such as checkpoint inhibitor chemotherapy combinations, work for months, not years,” said Barker’s thoracic oncologist Ben Creelan, MD. “The gold standard for Deborah’s cancer has a median progression-free survival of seven months. So, I think TIL therapy is an attractive option to seriously consider for patients like her.”
Barker was one of the first women to work outside the administrative offices in a Florida brewery.
A new unapproved treatment option didn’t scare Barker. She was a groundbreaker — one of the first women to work outside the administrative offices in a Florida brewery. After starting as a lab technician at what was then the Joseph Schlitz Brewing Company in Tampa in 1974, she went back to school for a degree in chemical engineering and eventually became the brewery’s first female brewmaster. That experience taught her a thing or two about perseverance.
“I didn’t carry any fear with me,” said Barker of her decision to join the clinical trial. “I didn’t hesitate for a moment because I felt like I didn’t have a choice.”
Unlocking Immune Response
Once Barker was enrolled in the trial, the first step was to harvest the immune cells inside her cancer. While she wouldn’t be a candidate for surgery in other circumstances because of her progressed disease, she underwent robotic surgery to remove cancerous lymph node tissue and a small portion of her lung that contained her primary tumor.
The T cells collected were sent to a lab to be multiplied, and Barker started receiving infusions of immunotherapy drug nivolumab. She responded so well to the initial treatment that doctors decided to hold off on TIL therapy.
“I was very happy I responded, but I was disappointed I wasn’t getting my cells right away,” said Barker.
However, after a year of stability, a scan showed disease progression in January 2019. Doctors told Barker it was time for her to receive her T cells.
After a round of inpatient chemotherapy, Barker was ready for her TIL infusion. She pulled from her experience with her sister’s transplant to get through the tough spots, but says she had very few severe side effects. After, she was placed back on nivolumab for another year, and besides a small disease progression that was treated with radiation, Barker has had clean scans ever since.
“Deborah’s immune cells were locked away inside her tumor so they weren’t able to completely eradicate the cancer on their own,” said Creelan. “But by pulling them out, growing them in large numbers and re-infusing them she’s clearly had an excellent response.”
Of the 16 patients on the trial, two — including Barker — had a complete response after TIL therapy. One theory why TIL works is because it spurs the growth of memory T cells, which stay in the body for decades to help patrol and prevent future cancer infections.
“Because there aren’t many good second-line treatment options for NSCLC, it’s hard to look a patient in the eyes and tell them standard treatment is worth doing when there isn’t a giant upside and we will probably be having the same discussion again in six months,” said Creelan. “Whereas with TIL therapy, there is a chance you can hit a home run. Obviously, Deborah has done that.”
TIL therapy is also a one-time treatment, reducing the length of time patients have to cope with intense therapy and unwanted side effects. Another benefit is that because the T cells come directly from the tumor, they can recognize many targets on cancer cells, making it even harder for cancer to hide or evade treatment. In Barker’s case, her T cells were able to recognize five unique mutations within her tumor.
TIL therapy is awaiting U.S. Food and Drug Administration approval in melanoma. Since Barker’s trial was the first to study the treatment in stage 4 NSCLC, a lot more research is needed in the lung cancer space. New data has shown TIL therapy response is better in NSCLC patients who have not had prior treatment and when it is combined with checkpoint inhibitors. For patients whose tumors cannot be easily removed, Moffitt is opening a trial that will use peripheral blood cells instead of T cells harvested from tumors for TIL therapy.
Land of the Living
Now that her cancer is in remission, Barker has returned to scuba diving.
The COVID-19 pandemic and becoming a caregiver for her mother delayed Barker’s return to the water, but after five years, she’s ready to put her scuba gear back on.
After her longtime dive partner, who Barker met at Schlitz in the ’70s, lost her own battle with cancer, Barker became involved with the Old Broads Dive Club out of California. She has scheduled two trips with them this spring: one to Cozumel and one to Little Cayman Island. Barker is more anxious about traveling than she is about the actual diving. She knows her lungs are ready.
“I felt like I had one foot in this world and one foot out,” said Barker. “Now, I feel like I am going to be around awhile so I need to get back to the land of the living.”
