Lifileucel — Drug Monograph

Brand names: Amtagvi

Drug class: Other

Mechanism of Action

Lifileucel is an autologous tumor-infiltrating lymphocyte (TIL) cell therapy derived from a surgically resected melanoma lesion. Following resection, TILs are expanded ex vivo from tumor fragments using rapid expansion protocols with high-dose IL-2 and feeder cells to generate a polyclonal, tumor-reactive T-cell population. These TILs contain endogenous T-cell receptors (TCRs) recognizing a broad array of tumor-specific neoantigens on melanoma cells — a fundamentally different mechanism from CAR-T constructs, as TILs use native TCR-MHC antigen recognition rather than MHC-independent CAR…

FDA Indications

• Unresectable or metastatic melanoma in adults who have received a prior anti-PD-1 therapy and, if BRAF V600 mutation-positive, a BRAF inhibitor with or without an MEK inhibitor (FDA approved February 16, 2024; based on C-144-01: 31.5% ORR)

Common Side Effects

• IL-2-associated: hypotension, chills, fever, fatigue, nausea, vomiting, diarrhea
• Lymphodepletion-related cytopenias (neutropenia, thrombocytopenia, anemia)
• Capillary leak syndrome
• Rash
• Decreased appetite
• Edema
• Elevated creatinine (IL-2)
• Oliguria

Clinical Pearl

Lifileucel is the first FDA-approved TIL therapy and the first approved cell therapy for a solid tumor. The 4–6 week manufacturing window requires careful disease burden assessment; bridging therapy may be needed. High-dose IL-2 requires ICU-capable administration and careful patient selection for cardiac and pulmonary fitness. Unlike CAR-T, TIL therapy leverages endogenous polyclonal TCR recognition of neoantigens, potentially overcoming tumor antigen escape seen with single-antigen-directed…

Related Therapies & Mechanisms

• MRNA-4157 (V940) personalized cancer vaccine (V940) — Other · Melanoma
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other
• Asparaginase (L-asparaginase, E. coli) (Elspar) — Other