April 22, 2024

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First TIL Therapy for Malignant Melanoma Approved

First TIL Therapy for Malignant Melanoma Approved

First TIL Therapy for Malignant Melanoma Approved

Recently, the U.S. Food and Drug Administration (FDA) accelerated the approval of Amtagvi (lifileucel), a tumor-infiltrating lymphocyte (TIL) therapy developed by Iovance Biotherapeutics, for the treatment of advanced melanoma.

This is the world’s first approved TIL therapy and also the first approved T-cell therapy for solid tumors, marking a milestone in the field!

First TIL Therapy for Malignant Melanoma Approved

Figure 1. FDA approves lifileucel for marketing

TIL Therapy: A Beacon of Hope for Melanoma Patients

Melanoma is a highly malignant tumor derived from melanocytes, commonly known as “malignant melanoma,” which mostly occurs on the skin but can also be found on mucous membranes and internal organs. In China, it is more common on the skin of the extremities (soles, toes, fingertips, and under the nails).

In recent years, the incidence and mortality rates of malignant melanoma have been increasing annually. Compared with other solid tumors, it leads to death at a younger age. It is noteworthy that the prognosis of advanced malignant melanoma is poor, mainly due to its high malignancy and propensity for metastasis. Any stimulation can promote tumor spread, leading to lymphatic and hematogenous metastasis in the late stage.

TILs exist in the interstitial tissue of tumor tissue and consist of heterogeneous cell populations including CD8+ T cells, CD4+ T cells, B cells, NK cells, and γδ T cells, among which the cytotoxic CD8+ T cells are mainly responsible for directly killing tumor cells. TIL therapy involves obtaining tumor tissue from patients, extracting TILs, and then stimulating their expansion in vitro using the cytokine IL-2. This in vitro stimulation not only increases the number of TILs but also activates their anti-tumor capabilities. Subsequently, these TILs are infused back into the patient’s body to more effectively kill tumor cells.

Lifileucel belongs to an autologous TIL therapy, which involves collecting infiltrating lymphocytes from the patient’s own tumor sample, expanding and culturing them in vitro, and then reinfusing them into the patient’s body to utilize the patient’s own immune system to recognize and destroy cancer cells.

The FDA approval of lifileucel this time is applicable to the treatment of adult patients with unresectable or metastatic melanoma who have previously received programmed cell death protein-1 (PD-1) antibody therapy, with or without BRAF inhibitor therapy in patients with BRAF V600-positive mutations. This marks the first and only time that personalized T-cell therapy has been approved by the FDA for the treatment of solid tumors.

C-144-01 Study Results: Nearly 80% of Melanoma Patients Experience Tumor Remission or Stability!

C-144-01 is a global, multicenter Phase II clinical trial. As of July 15, 2022, a total of 153 advanced melanoma patients received lifileucel treatment in this study, which was divided into 4 cohorts: Cohort 1 patients received non-cryopreserved TIL products; Cohorts 2 and 4 patients received cryopreserved TIL treatment; Cohort 3 consisted of patients who received repeated TIL treatment. The median follow-up time was 36.5 months (over 3 years).

First TIL Therapy for Malignant Melanoma Approved

Figure 2. C-144-01 test design

The results showed that the efficacy of lifileucel was relatively long-lasting. As assessed by the independent imaging review committee (IRC), the objective response rate (ORR) was 34.8% in Cohort 2, 28.7% in Cohort 4, and the total ORR in Cohorts 2+4 was 31.4%, including 8 patients achieving complete remission (CR) and 40 patients achieving partial remission (PR).

Table 1.C-144-01 research results

First TIL Therapy for Malignant Melanoma Approved


Since its first clinical attempt in 1988, the development of TIL therapy has spanned decades.

The approval of lifileucel this time has brought hope to patients with advanced melanoma who have deteriorated after standard treatment, marking a significant advancement in the field of immunotherapy using one’s own immune cells to combat cancer.

More and more doctors will have the ability to provide “personalized” and “tailored” treatment plans to suitable individuals.

This one-time cell therapy represents a promising innovation in the field of melanoma treatment, and lifileucel will become a new option for the treatment of advanced melanoma.

First TIL Therapy for Malignant Melanoma Approved


[1]. Iovance’s Amtagvi (lifileucel) receives US FDA accelerated approval for advanced melanoma. News release. Iovance. February 16, 2024. Accessed February 16, 2024. https://ir.iovance.com/news-releases/news-release-details/iovances-amtagvitm-lifileucel-receives-us-fda-accelerated

[2]. Chesney J, Lewis KD, Kluger H, Hamid O, et al. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022;10(12):e005755.

(source:internet, reference only)

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