C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed
Immune cells harvested from a patient's tumour, expanded in the lab and reinfused shrank melanoma in 36% of patients whose disease had progressed on PD-1 blockade, with responses that mostly lasted.
Cohort 2 of the C-144-01 phase 2 trial treated 66 patients with advanced melanoma that had progressed after anti-PD-1 therapy (and BRAF/MEK inhibitors where indicated; median 3.3 prior lines) with a single infusion of lifileucel, autologous tumour-infiltrating lymphocytes expanded centrally over about 22 days, after non-myeloablative lymphodepletion and followed by up to six doses of high-dose interleukin-2. The objective response rate was 36% (2 complete, 22 partial) with disease control in 80%; median duration of response was not reached at 18.7 months of follow-up. Adverse events were largely attributable to lymphodepletion and IL-2 and resolved within two weeks, with two treatment-related deaths. Pooled analysis of 153 patients from cohorts 2 and 4 showed a 31% response rate and supported FDA accelerated approval in February 2024, the first TIL therapy and first cell therapy for a solid tumour.
- 66 patients with anti-PD-1-refractory advanced melanoma; median 3.3 prior therapies; single lifileucel infusion after cyclophosphamide-fludarabine lymphodepletion, then up to 6 doses of high-dose IL-2.
- Objective response 36% (3% complete); disease control 80%.
- Median duration of response not reached at 18.7 months; responses deepened over time in some patients.
- Grade 3-4 adverse events mostly cytopenias, febrile neutropenia and IL-2-related hypotension, resolving within 2 weeks; 2 treatment-related deaths.
- Pooled cohorts 2 and 4 (153 patients): objective response 31.4%, supporting accelerated approval in 2024.
Lifileucel proved that Steven Rosenberg's decades-old TIL concept could be industrialised into a licensed product and gave patients with checkpoint-refractory melanoma, who otherwise have few options, a chance of durable remission. It is the first cell therapy approved for any solid tumour. The treatment requires surgery to harvest tumour, hospitalisation for lymphodepletion and IL-2, and specialised centres, so its reach is limited.
- Single-arm trial; approval rested on response rate rather than survival.
- Toxic conditioning and high-dose IL-2 make the regimen unsuitable for frail patients.
- Manufacturing takes about three weeks and needs a resectable lesion; not all patients yield a product.
- Cost (list price above 500,000 US dollars) and centre requirements restrict access.
Afami-cel showed that T cells can be redirected against an intracellular cancer antigen, something CAR-T cannot do, and produced meaningful responses in a rare sarcoma with few options. It opens a path to TCR-T against other shared antigens and neoantigens. Restriction to one HLA type and one antigen, plus complex manufacturing, means it will help a small, defined group.
This trial supplied the randomised proof that was missing for TIL therapy and showed academic centres can run cell-therapy phase 3 trials without industry. It supports TIL as a standard option after checkpoint inhibitor failure in melanoma and underpinned reimbursement in the Netherlands. The comparator, ipilimumab, is itself only modestly effective in this setting, and overall survival did not differ significantly.
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not linked directly; found by shared links- IdeaSelect patients for cell therapy by whether their tumour holds reactive T cells
Shares Iovance Biotherapeutics, Lifileucel, Tumour-infiltrating lymphocytes (TILs), TIL therapy.
- IdeaUse patient organoids to check a cell therapy will work before infusing it
Shares Iovance Biotherapeutics, Lifileucel, TIL therapy, Manufacturing cost and time for living and radioactive medicines.
- PersonJohn Haanen
Shares Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma, Lifileucel, TIL therapy, Melanoma.
- PersonShari Pilon-Thomas
Shares Moffitt Cancer Center, TIL therapy, Melanoma.
- PairingPD-1 failure → TIL therapy
Shares Lifileucel, TIL therapy, Melanoma.
- InstitutionNCI Center for Cancer Research (intramural programme)
Shares Aldesleukin (high-dose IL-2), Steven A. Rosenberg, TIL therapy, National Cancer Institute (NIH).
- PersonPatrick Hwu
Shares Moffitt Cancer Center, TIL therapy, Melanoma.
- IdeaGrow tumour organoids together with the patient's own immune cells
Shares Tumour-infiltrating lymphocytes (TILs), TIL therapy, No one can predict who responds to immunotherapy.