Iovance TIL therapy, marketed as Amtagvi (lifileucel), is a personalized immunotherapy that uses a patient’s own immune cells to fight cancer. This treatment is considered a “living drug” because the therapeutic agent is composed of living T cells. The U.S. Food and Drug Administration (FDA) has approved Amtagvi for adults with advanced melanoma that cannot be surgically removed or has spread to other parts of the body. It is intended for patients whose cancer has progressed after other treatments, including PD-1 blocking antibodies, and uses naturally occurring, not genetically modified, immune cells.
The Science Behind TIL Therapy
The foundation of this therapy lies in immune cells called Tumor-Infiltrating Lymphocytes (TILs). These are T cells that have naturally penetrated a tumor, showing they can recognize and engage with cancer cells. A portion of the patient’s tumor is surgically removed to serve as the source material for these TILs.
In the laboratory, technicians separate the TILs from the tumor tissue, isolating the immune cells that have already shown an interest in the cancer. These selected lymphocytes are then cultured in a controlled environment, a process known as ex vivo expansion. Over several weeks, they are stimulated to multiply into the billions.
The expansion phase selectively grows the T cells most adept at recognizing the specific mutations in the patient’s cancer. The final product is a concentrated infusion containing billions of the patient’s own T cells, prepared to attack the tumor. This personalized batch is then cryopreserved and sent back to the hospital for infusion.
The Patient Treatment Process
The patient’s journey with TIL therapy is a multi-step clinical process requiring hospitalization. The process starts with the surgical resection of a tumor, which is sent to an Iovance manufacturing facility to create the personalized infusion. While the cells are grown over several weeks, the patient waits for the treatment to be prepared.
When manufacturing is complete, the patient is admitted to a treatment center for lymphodepletion chemotherapy. This regimen, with drugs like cyclophosphamide and fludarabine, reduces existing lymphocytes in the body. This makes space for the newly infused TILs, helping them proliferate and attack the cancer.
After chemotherapy, the patient receives the one-time infusion of their personalized Amtagvi product. Within 24 hours, they begin a short course of interleukin-2 (IL-2), a protein that stimulates the new TILs’ activity and expansion. This part of the treatment requires a hospital stay for close monitoring.
Clinical Applications and Effectiveness
Amtagvi has FDA accelerated approval for adults with unresectable or metastatic melanoma. Patients must have previously undergone treatment with a PD-1 blocking antibody. If their tumor has a BRAF V600 mutation, they also must have been treated with a BRAF inhibitor.
Effectiveness was shown in the C-144-01 clinical trial. The objective response rate (ORR), which measures the percentage of patients whose tumors shrank, was 31.5%. For those who responded, the results were often durable, with the median duration of response not reached at the time of initial analysis. Long-term follow-up data showed a median overall survival of 13.9 months.
Success in melanoma has prompted further research into TIL therapy’s potential for other cancers. Iovance is investigating its use for solid tumors like non-small cell lung cancer. The company is also studying its use in combination with other drugs for earlier stages of melanoma.
Managing Side Effects and Risks
The Amtagvi regimen has risks detailed in an FDA Boxed Warning, many stemming from the pre-infusion chemotherapy. The lymphodepleting regimen weakens the immune system, leading to prolonged low blood cell counts (cytopenia). This condition increases the risk of severe infections.
The TIL therapy and subsequent IL-2 administration also have potential complications. The Boxed Warning highlights risks of treatment-related mortality, severe infection, and cardiopulmonary or renal impairment. Common adverse reactions include:
- Chills
- Fever
- Fatigue
- Rapid heart rate
- Diarrhea
- Low blood pressure
These side effects often require intensive medical management.
Due to the complexity and severity of potential side effects, Amtagvi is only administered at authorized treatment centers. These facilities have the specialized expertise and resources to manage complications associated with lymphodepleting chemotherapy and high-dose IL-2. Careful patient monitoring during and after treatment is a standard part of the protocol.