Loading
Immunotherapy and Immune Responses / CAR-T Cell Therapy Research · Journal article
Journal of Translational Medicine · August 11, 2026
Early or partial results. Treat as a signal, not a conclusion.
This phase 1 trial reports feasibility and preliminary clinical activity of autologous TIL therapy in 12 Asian patients with advanced solid tumors, achieving a 33.3% ORR and 75% DCR, alongside mechanistic observations that ASS1 and CEP20 knockout enhances TIL function in preclinical models. The findings are exploratory and hypothesis-generating; the small, heterogeneous, uncontrolled sample and reliance on in vitro and xenograft validation of targets preclude clinical practice change and require confirmation in larger, controlled studies.
Phase 1, single-arm, investigator-initiated trial. Twelve patients with advanced melanoma, cervical, lung, or head and neck cancers who had progressed after standard therapies; enrolled between August 2022 and December 2024.. Intervention: Autologous TIL therapy: lymphodepletion (cyclophosphamide 30 mg/kg × 2 days, fludarabine 25 mg/m² × 5 days) followed by intravenous infusion of autologous TIL and high-dose IL-2 (6–12 days).. n = 12. Not stated in source..
Objective response rate (ORR) 33.3% (4/12 patients), including 1 complete response and 3 partial responses Disease control rate (DCR) 75% (9/12 patients) Most common adverse events: fever, anemia, nausea, hypertension, hyponatremia
No long-term survival, progression-free survival, or duration of response reported; follow-up duration unclear beyond 28-day safety window Most common adverse events: fever, anemia, nausea, hypertension, hyponatremia
These findings suggest TIL therapy may have activity beyond melanoma in diverse solid tumors; however, the small uncontrolled sample precludes clinical recommendation. Identification of ASS1 and CEP20 as negative regulators is mechanistically interesting but requires validation in prospective, larger trials before informing clinical enhancement strategies.
Phase 1 investigator-initiated trial in 12 patients with heterogeneous solid tumors, showing feasibility and a 33.3% response rate, but underpowered for efficacy claims and mechanistic findings rely on uncontrolled in vitro and in vivo knockout experiments.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest TIL therapy may have activity beyond melanoma in diverse solid tumors; however, the small uncontrolled sample precludes clinical recommendation. Identification of ASS1 and CEP20 as negative regulators is mechanistically interesting but requires validation in prospective, larger trials before informing clinical enhancement strategies.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated clinical potential in melanoma; however, its applicability across diverse solid tumors in Asian patients remains unclear. Identification of molecular targets to enhance the antitumor activity of TIL is urgently needed. In a phase I investigator-initiated trial, we evaluated the safety, feasibility, and preliminary efficacy of autologous TIL therapy in twelve patients with advanced melanoma, cervical, lung, or head and neck cancers. Twelve patients who had progressed after standard therapies were enrolled between August 2022 and December 2024. Patients received lymphodepletion with cyclophosphamide (30 mg/kg) for 2 days, followed by fludarabine (25 mg/m²) for 5 days, approximately 24 h before intravenous infusion of autologous TIL. High-dose interleukin-2 (IL-2) was administered for 6–12 days to support T-cell survival and expansion. After a 28-day safety observation period, tumor assessments were performed every 6 weeks for the first 6 months and thereafter every 12 weeks during long-term follow-up, according to RECIST 1.1 criteria. T cell receptor (TCR) sequencing was conducted to evaluate in vivo persistence of infused TIL. Differential gene expression analysis was performed using bulk RNA sequencing on TIL from responders and non-responders. Target gene knockout in TIL was achieved using CRISPR/Cas9 technology to assess enhancement of antitumor function. The most common adverse events were fever, anemia, nausea, hypertension, and hyponatremia. The objective response rate (ORR) was 33.3% (4/12), including one complete response (CR) and three partial responses (PR), with a disease control rate (DCR) of 75% (9/12). Infused TIL persisted in peripheral blood and induced a reversal in the peripheral CD4 + T to CD8 + T cell ratio. TCR sequencing revealed dynamic clonal remodeling in responders. Transcriptomic profiling identified ASS1 and CEP20 as genes negatively associated with therapeutic efficacy. CRISPR/Cas9-mediated knockout of ASS1 or CEP20 enhanced TIL memory phenotypes, cytokine production, and tumor cytotoxicity both in vitro and in vivo. This study demonstrates the efficacy of TIL therapy in diverse solid tumors among Asian patients, reveals dynamic TCR clonal remodeling in responders, and identifies ASS1 and CEP20 knockout as strategies to potentiate antitumor activity. These findings provide mechanistic insights that may guide improvement of TIL therapy for broader clinical application. Trial registration: NCT, NCT05366478. Registered 01 August 2022, http://www.clinicalTrial.gov/NCT05366478. TIL therapy shows clinical activity in diverse solid tumors of Asian patients with a 33.3% objective response rate (ORR) and 75% disease control rate (DCR). T cell receptor (TCR) sequencing revealed dynamic clonal remodeling correlates with efficacy of TIL therapy. Transcriptomic profiling identifies ASS1 and CEP20 as negative regulators of TIL function. CRISPR/Cas9-edited TIL exhibit enhanced persistence, cytokine secretion, and tumor control in vivo and in vitro. This study links clinical and molecular findings to enable reverse translational improvement of TIL therapy.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.