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NOT YET RECRUITING
NCT07329959
PHASE1

CAR-DC for End-Stage IPF

Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

View on ClinicalTrials.gov

Summary

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal interstitial lung disease characterized by irreversible scarring, leading to respiratory failure. With limited treatment options and a poor prognosis, new therapies are urgently needed. This study investigates a novel cell therapy targeting pathological fibroblasts, a key driver of fibrosis. Single-cell analyses identify CTHRC1+FAP+ fibroblasts as a collagen-producing subpopulation crucial in IPF progression. Chimeric antigen receptor (CAR) technology enables precise targeting of these cells. While CAR-Treg therapy has shown promise in preclinical models, its clinical translation requires careful safety evaluation regarding infection risk, potential tumor promotion, and immune reconstitution. This trial employs an innovative approach using engineered dendritic cells (DCs). CAR technology is applied to generate immunosuppressive CAR-DCs (iCAR-DCs) designed to target FAP, localize to fibrotic lung areas, and attenuate fibrosis without eliciting a detrimental immune response. Preliminary mouse studies demonstrated that iCAR-DC administration following lung injury significantly reduced fibrosis without apparent organ toxicity and improved survival. This single-arm trial aims to evaluate the efficacy and safety of this immunosuppressive CAR-DC therapy in patients with end-stage IPF. Key assessments will include changes in lung function, fibrosis extent on imaging, and comprehensive monitoring of potential adverse effects, particularly infections, tumor markers, and immune parameters.

Official title: Safety and Efficacy of Immunosuppressive CAR-DC Targeting FAP in the Treatment of End-stage Idiopathic Pulmonary Fibrosis

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

8

Start Date

2026-02-01

Completion Date

2029-02-28

Last Updated

2026-01-09

Healthy Volunteers

No

Interventions

PROCEDURE

Leukapheresis

Subjects will be hospitalized in the Lung Transplant Ward to undergo leukapheresis, followed by an observation period. Eligible subjects, after signing the specific leukapheresis consent form, will undergo apheresis for the collection of approximately 100 ml of blood using a blood cell separator for the preparation of CAR-DC reagents.

BIOLOGICAL

CAR-DC

Subjects will be hospitalized to receive autologous FAP-targeted immunosuppressive CAR-DC cell therapy, followed by an observation period. Based on our team's preclinical studies, the starting dose was determined to be 4×10⁵ cells/kg. This trial will employ a standard "3+3" dose-escalation design: Dose Level -1 at 1×10⁵ cells/kg, Dose Level 1 (starting dose) at 4×10⁵ cells/kg, and Dose Level 2 at 8×10⁵ cells/kg. The 3+3 dose escalation begins with the Dose Level 1 administered to a cohort of three subjects. If no dose-limiting toxicities (DLTs) are observed, the dose is escalated for the next cohort. If one DLT occurs, the cohort is expanded to six subjects at the same dose; escalation proceeds only if no further DLTs are seen in the expanded cohort. If two or more DLTs occur at any point within a cohort, dose escalation stops, and the maximum tolerated dose (MTD) is defined as the highest dose level with an observed DLT rate of less than 2 out of 6 subjects.