Second opinion on TIL Therapy

TIL therapy (Tumor-Infiltrating Lymphocyte therapy) is a personalized form of cellular immunotherapy that uses the patient’s own immune cells to fight cancer. T lymphocytes are isolated from a sample of the patient’s tumor, expanded to very large numbers in a specialized laboratory, and then returned to the patient through an intravenous infusion. The approach is designed to increase the number of naturally occurring tumor-reactive immune cells capable of recognizing and attacking malignant cells.

What are tumor-infiltrating lymphocytes?

Lymphocytes are immune cells that play an important role in protecting the body against infections and abnormal cells. Among them, T lymphocytes are particularly important for adaptive anti-tumor immunity because they can recognize specific antigens associated with malignant cells and contribute to their destruction.

Tumor-infiltrating lymphocytes (TILs) are immune cells that have migrated from the bloodstream into a tumor and its surrounding microenvironment. TILs are a heterogeneous population and may include different subsets of T cells and B cells, as well as other immune-cell populations. In the context of TIL therapy, the main therapeutic focus is on tumor-reactive T lymphocytes.

Important TIL populations include:

• CD8+ cytotoxic T cells, which can directly kill tumor cells carrying antigens recognized by their T-cell receptors;
• CD4+ helper T cells, which coordinate immune responses and can support anti-tumor activity;
• regulatory T cells (Tregs), which suppress immune responses and may contribute to an immunosuppressive tumor microenvironment;
• B cells and natural killer (NK) cells, which can also be present in tumors, although conventional TIL therapy primarily focuses on tumor-reactive T cells.

One of the key features of tumor-infiltrating is that these cells have already encountered the tumor in the patient’s body. Consequently, the tumor may contain T-cell clones capable of recognizing antigens that are specific to, or enriched in, that individual cancer.

How is TIL therapy performed?

TIL therapy is a complex, multi-step treatment that requires specialized surgical, laboratory and oncology facilities.

1. Tumor tissue collection

The first step is the surgical removal of a portion of the patient’s tumor. The tissue must contain lymphocytes that can potentially be used to manufacture the personalized cell therapy.

The location and amount of tissue required depend on the type and location of the cancer. When several tumor sites are available, the treatment team determines which lesion is most suitable for collection.

2. Isolation and expansion of TILs

The tumor specimen is transported to a specialized cell-manufacturing facility. T cells are separated from the tumor tissue and stimulated to proliferate outside the body.

This process transforms a relatively small tumor specimen into a therapeutic cell product containing billions of T cells.

3. Lymphodepleting chemotherapy

Before the expanded TILs are infused, the patient receives lymphodepleting chemotherapy. The purpose is to temporarily reduce the patient’s existing lymphocyte population and create a more favorable environment for the transferred cells to expand and function.

4. TIL infusion

Once lymphodepletion is completed, the patient receives the individualized TIL product intravenously.

5. Interleukin-2 support

After TIL infusion, interleukin-2 (IL-2, aldesleukin) is administered to support the activity and expansion of the transferred T cells in the patient’s body.

Advantages of TIL therapy

TIL therapy has several characteristics that distinguish it from other forms of cancer immunotherapy.

• Personalized treatment. The therapy is manufactured from the patient’s own immune cells obtained directly from their tumor.
• Natural tumor reactivity. TILs have already migrated into the tumor and may contain T-cell clones capable of recognizing tumor-associated or patient-specific cancer antigens.
• Large-scale cell expansion. Laboratory manufacturing can increase the number of tumor-reactive T cells from a relatively small tumor specimen to billions of cells.
• Potential activity after other treatments have failed. The strongest clinical evidence to date has been generated in advanced melanoma, including patients whose disease has progressed after previous immunotherapy.
• Potential for durable responses. Clinical studies have demonstrated objective and, in some patients, complete responses that can persist for prolonged periods following TIL therapy.

TIL therapy, however, is not suitable for every patient or every type of cancer. Treatment feasibility depends on tumor biology, the availability of suitable tumor tissue, the patient’s general condition and access to specialized cellular-therapy infrastructure.

Possible side effects

The safety profile of TIL therapy is influenced by all components of the treatment, including lymphodepleting chemotherapy, the TIL infusion itself and subsequent IL-2 administration.

Potential side effects include:

• fever and chills;
• fatigue and weakness;
• reduced white blood cell and neutrophil counts;
• anemia and other blood-count abnormalities;
• low blood pressure;
• rapid heart rate;
• nausea, vomiting and diarrhea;
• skin rash;
• fluid retention and edema;
• increased risk of infections;
• shortness of breath and reduced blood oxygen levels.

The treatment therefore requires specialized inpatient care and close monitoring.

Approved indications for TIL therapy

The major regulatory milestone for TIL therapy has been the approval of lifileucel (Amtagvi), the first commercially manufactured TIL-based cellular therapy.

In the United States, the FDA approved lifileucel in 2024 for adult patients with unresectable or metastatic melanoma whose disease has previously been treated with a PD-1 blocking antibody. For patients with BRAF V600-positive melanoma, prior treatment with a BRAF inhibitor with or without a MEK inhibitor is also required. The U.S. approval was granted under the accelerated approval pathway.

In Canada, Amtagvi received a conditional authorization in 2025 for adults with unresectable or metastatic melanoma that has progressed during or after at least one prior systemic treatment including a PD-1 blocking antibody and, when BRAF V600-positive, a BRAF inhibitor with or without a MEK inhibitor, in patients who have no satisfactory alternative treatment options.

In addition to melanoma, TIL therapy has demonstrated efficacy in the treatment of non-small cell lung cancer, breast cancer, cervical cancer, and ovarian cancer. For these cancer types, TIL therapy is currently available primarily through clinical trials or specialized academic programs.

Where is TIL therapy available?

TIL therapy is being developed and provided in a growing number of countries. However, it is important to distinguish between commercially approved TIL products and academic or clinical-trial TIL programs.

The most established commercial TIL treatment pathway is currently in the United States, where lifileucel is administered through specialized Authorized Treatment Centers.

Lifileucel has also received regulatory authorization in Canada and Australia.

Israel has substantial clinical experience with TIL therapy. The Sheba Medical Center’s Ella Lemelbaum Institute, for example, has developed TIL-based treatment programs for advanced melanoma over many years.

In Europe, important TIL research and treatment programs have been developed in the Netherlands and Denmark. The Netherlands Cancer Institute has played a major role in the clinical development of TIL therapy and in randomized studies comparing TIL treatment with standard immunotherapy.

European TIL research is also being conducted in Spain, France, Sweden and Switzerland.

For international patients, access may be possible through a commercially approved program, an academic treatment protocol or a clinical trial, depending on the cancer type, eligibility criteria and regulatory framework of the country.

TIL Therapy in China

China has become one of the most active countries in the development and clinical research of TIL therapy. Chinese cancer centers are working on introducing autologous TIL therapies for advanced melanoma and other solid tumors, including lung cancer, breast cancer, cancer of the cervix and ovaries. Chinese research groups are also developing next-generation TIL approaches designed to shorten manufacturing time, reduce dependence on high-dose IL-2 and improve treatment efficacy. For example, in 2026, results from a multicenter Chinese Phase II study of GC101 TIL in advanced melanoma were presented at the ASCO Annual Meeting; the study involved 25 clinical sites across China. Another Chinese approach, FAST-TIL (HS-IT101), is being investigated as a rapidly manufactured TIL product that can be produced in approximately 14 days using less than 0.05 g of starting tumor tissue. TIL clinical programs and trials are being conducted at major oncology centers in Beijing, Shanghai, Tianjin, Guangzhou, Chengdu and other Chinese cities.

Potential future indications for TIL therapy

One of the main goals of current TIL research is to extend the therapy beyond melanoma, e.g., for head and neck squamous cell carcinoma, urothelial and colorectal carcinoma.

Another important research direction is the optimization of TIL products themselves. Scientists are investigating methods for selecting the most active tumor-reactive T-cell populations, genetically modifying TILs, improving their persistence and metabolic fitness, combining TIL therapy with immune checkpoint inhibitors, and reducing the toxicity associated with lymphodepletion and IL-2.

Researchers are particularly interested in cancers that have limited responses to currently available immunotherapies. The long-term goal is to make personalized tumor-reactive T-cell therapy effective for a much broader range of solid tumors.