Tumor-infiltrating lymphocyte (TIL) therapy represents a personalized approach to cancer treatment, leveraging the body’s own immune system to combat malignant cells. This innovative immunotherapy involves isolating specific immune cells, known as TILs, directly from a patient’s tumor. These cells are then expanded in a laboratory to vastly increase their numbers before being reintroduced into the patient. The goal is to empower the immune system with a more robust and targeted force to identify and eliminate cancer cells throughout the body.
How TIL Cell Therapy Works
The process of TIL cell therapy begins with the surgical removal of a small portion of the patient’s tumor tissue, typically between 1.5 and 4 centimeters in size. This sample is then transported to a specialized laboratory where tumor-infiltrating lymphocytes (TILs), a type of T lymphocyte, are separated. These immune cells are naturally found within tumors and have already begun to recognize and attack cancer cells.
Once isolated, these TILs are multiplied in the laboratory, a process that can take approximately four to six weeks. During this expansion, the TILs are grown to billions in number, often with the aid of interleukin-2 (IL-2), which promotes their rapid growth. This expansion aims to create a sufficiently large population of these cancer-fighting cells.
Before the expanded TILs are reinfused, the patient undergoes a conditioning regimen, typically involving several days of chemotherapy. This chemotherapy, often a combination of cyclophosphamide and fludarabine, reduces the patient’s existing immune cells, creating space for the newly infused TILs to engraft and expand.
Within 24 hours of completing the conditioning chemotherapy, the expanded TILs are administered into the patient through an intravenous infusion. Following this, patients may also receive a short course of high-dose IL-2. This additional IL-2 stimulates the activity and survival of the reinfused TILs, enhancing their ability to seek out and destroy cancer cells. These reinfused TILs recognize a multitude of immune markers on cancer cells, allowing them to target and eliminate malignant cells while generally leaving healthy cells unharmed.
Cancers Treated with TIL Therapy
TIL cell therapy has shown promise, particularly in treating metastatic melanoma, a severe form of skin cancer that has spread. It has received U.S. Food and Drug Administration (FDA) approval for melanoma that has progressed despite other treatments, including PD-1 blocking antibodies. Objective response rates in heavily pretreated patients with metastatic melanoma have consistently ranged between 30% and 50% in clinical trials.
Beyond melanoma, researchers are investigating TIL therapy for its potential application in other solid tumors. Clinical trials are exploring its effectiveness in various cancers, including lung cancer, head and neck squamous cell carcinoma, cervical cancer, and genitourinary cancers. TIL therapy has also led to tumor regression in individual patients with advanced colon and breast cancer in clinical trials.
The effectiveness of TILs against solid tumors stems from their ability to penetrate the tumor microenvironment. These cells are naturally present within tumors, recognizing and infiltrating cancerous tissue. Unlike some other cell therapies that might target a single protein, TILs can recognize a broader range of tumor-associated antigens, making them more adaptable to the diverse nature of solid tumors. Research aims to expand the applications of TIL therapy, exploring its use in other solid tumor types like ovarian cancer and colorectal cancer.
Patient Experience and Considerations
Patient suitability for TIL therapy involves several factors, including the specific type of cancer and the patient’s overall health. Patients need to have a tumor of at least 1.5 centimeters from which TILs can be harvested. They also need to be fit enough to tolerate the high-dose chemotherapy regimen that precedes the TIL infusion, similar to doses given before a bone marrow transplant.
The entire treatment journey, from tumor biopsy to recovery, can span several weeks. Following cell expansion, patients undergo a five to seven-day course of lymphodepleting chemotherapy, followed by the TIL infusion. Patients can expect an extended inpatient hospital stay, often lasting two to three weeks, in a specialized center equipped for intensive care, due to the need for close monitoring of side effects.
Potential side effects associated with TIL therapy primarily arise from the conditioning chemotherapy and the subsequent administration of IL-2. Common side effects from chemotherapy include low blood counts (leading to increased risk of infection, bleeding, and anemia), hair loss, mouth sores, and diarrhea. The TIL infusion itself may cause acute reactions such as fever, chills, fatigue, rash, and shortness of breath. Patients remain highly immunocompromised for weeks after the infusion, necessitating strict infection control measures.
Medical teams provide close monitoring and supportive care, including prophylactic antimicrobials and blood transfusions, to manage these effects. Recovery involves continued monitoring of blood counts and organ function, along with long-term follow-up appointments to assess treatment response and manage any lingering adverse events.