The field of cancer cell and gene therapy revolves around one simple concept: modifying the body’s own immune cells to maximize their ability to fight cancer. Over the last two decades, it’s an approach that has led to breakthrough successes in treating blood cancers with CAR T cells. But another type of immune cell has shown particular promise in treating solid tumors and is FDA-approved for metastatic melanoma, with active trials for other solid tumors, including pancreatic cancer. That immune cell is the tumor-infiltrating lymphocyte, or TIL, whose study is moving the field of cell and gene therapy in bold new ways.
What are tumor-infiltrating lymphocytes or TILs?
TILs are white blood cells made in the bone marrow that move from the bloodstream into a solid tumor to fight cancer. These can be either T cells or B cells and play a role in the immune system’s natural response to cancer.
Despite their cancer-fighting ability, TILs usually do not breach a solid tumor in enough numbers to destroy a cancer on their own, and over time become exhausted and ineffective. However, their ability to detect and respond to cancer antigens has made them the focus of a cancer cell therapy called TIL therapy.
How can TILs be used in cancer therapy?
TIL therapy attacks cancer by isolating and amplifying the effects that a person’s natural TIL response has on a tumor. In TIL therapy, scientists collect a piece of a patient’s tumor, separate the TILs from the sample, and then multiply the cells in a laboratory. Afterward, the expanded TILs are re-infused into the patient to attack the cancer in much greater numbers.
Major breakthroughs in TIL therapy have been made in recent years, culminating in the FDA approval of Amtagvi (lifileucel) for the treatment of melanoma in 2024. Not only was lifileucel the first TIL therapy approved for cancer treatment, but it was also the first cell therapy approved for the treatment of a solid tumor of any kind. This marked a monumental step forward for the field of cancer cell and gene therapy and for patients who need better treatment options.
Chris White tried nearly every possible treatment option available to beat his rare and aggressive melanoma. Yet, after three surgeries, multiple rounds of chemotherapy, and three attempts with immunotherapy, he was told to consider hospice care and get his end-of-life affairs in order. That was December 2019. Remarkably, today, Chris is cancer-free – thanks to TIL therapy.
Recent advancements in TIL therapy.
The success of TIL therapy in treating melanoma has led researchers to look outward, conducting numerous studies on its application to other cancers. Over the last two years, this research has led to a series of promising results that bode well for the future of TIL therapy for cancer.
The year 2025 was marked by ongoing progress in the TIL space. In April, the National Institutes of Health (NIH) published data showing objective responses to TIL therapy in patients with metastatic gastrointestinal cancers, including pancreatic cancer. The study’s lead investigator, Steven A. Rosenberg, MD, PhD, was honored by ACGT with the Edward Netter Leadership Award at its 2025 Gala Awards Luncheon.
Iovance Biotechnology, the company that developed lifileucel, reported results from a Phase 2 study showing the promising efficacy of a one-time TIL therapy for advanced non-small cell lung cancer (NSCLC), the most common form of lung cancer. Iovance is also enrolling patients in the IOV-END-201 Phase 2 trial, which is investigating lifileucel for advanced endometrial cancer patients whose cancer has progressed after chemotherapy and checkpoint immunotherapy.
Although further development is needed before TIL therapies are approved in some of these areas, these studies show that TIL therapy is on the cusp of becoming a game-changing cancer treatment. For a more in-depth conversation on the history and potential of TIL therapy, listen to this podcast interview between ACGT Research Fellow Joseph Fraietta, PhD (University of Pennsylvania), and ACGT Scientific Advisory Council Chair Michael T. Lotze, MD (University of Pittsburgh).
What’s on the horizon?
Researchers aren’t just developing TIL therapies for new types of cancer – they’re also improving the effectiveness of what they already have. The subset of patients able to receive lifileucel for melanoma is limited due to the procedure’s intensive nature. Toxicity levels also pose a challenge. Researchers continue to explore ways to improve efficacy, reduce toxicity, and identify combinations with other immunotherapies that will make this type of treatment more accessible for all.
Now is the time to keep the momentum going. ACGT asks you to join our Alliance of scientists, patients, biotech leaders, and donors. The last group is the most important, as none of ACGT’s funding of innovative research programs would be possible without the support of our donors.
Please donate today to help ACGT support TIL therapy researchers and others who believe in cell and gene therapy as a potential cure for cancer. If you’ve enjoyed reading this latest news about cell and gene therapy, sign up for our monthly email newsletter to receive more updates directly to your inbox about this emerging field of cancer treatment.
