CAR-DC for End-Stage IPF
ConditionIdiopathic Pulmonary Fibrosis(IPF)
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorSecond Affiliated Hospital, School of Medicine, Zhejiang University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
A decline in forced vital capacity (FVC) ≥10% over a 6-month follow-up period.
A decline in diffusing capacity of the lungs for carbon monoxide (DLCO) ≥10% of predicted value over 6 months.
Six-minute walk test results showing oxygen saturation <88%, a distance walked <250 meters, or a decline of >50 meters in distance over 6 months.
Presence of pulmonary hypertension (PH) confirmed by right heart catheterization or transthoracic echocardiography.
Disqualifiers
History of acute exacerbation of IPF within 4 weeks prior to screening or during the screening period.
Presence of interstitial lung disease (ILD) other than IPF, including but not limited to: other forms of idiopathic interstitial pneumonia; ILD associated with fibrogenic agents, environmental exposures, or drug toxicity; other occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; or ILD related to systemic diseases (e.g., vasculitis, infections such as tuberculosis, connective tissue diseases). Cases with uncertain diagnosis require serological testing and/or multidisciplinary team review for confirmation.
Presence of significant active infection.
History of malignancy, except for malignancies treated with curative intent and with no recurrence for ≥5 years, resected basal cell or squamous cell skin carcinoma, carcinoma in situ of the cervix, or resected colonic polyps.
Trial design
Design model
Single group
Treatments tested in this trial
Leukapheresis
Procedure/SurgerySubjects 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.
CAR-DC
Biological/VaccineSubjects 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.
Treatment groups
8 Participants
are divided into 1 treatment groupGroup A: CAR-DC TreatmentExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
The safety and efficacy of targeted FAP immunosuppressive CAR-DC in the treatment of end-stage idiopathic pulmonary fibrosis
The incidence of dose-limiting toxicity (DLT) and treatment-related adverse events (TEAE) within 14 days was evaluated in the targeted FAP immunosuppressive CAR-DC therapy for end-stage idiopathic pulmonary fibrosis.
Time frame
Within six months after CAR-DC therapySecondary outcomes
1
The difference in forced vital capacity compared to the baseline before treatment
Time frame
The three time points following CAR-DC cell therapy: Month 1, Month 3, and Month 6.2
The difference in pulmonary carbon monoxide diffusion capacity compared to the baseline before treatment
Time frame
The three time points following CAR-DC cell therapy: Month 1, Month 3, and Month 6.3
The difference between the ratio of forced expiratory volume in the first second and forced vital capacity compared to the baseline before treatment
Time frame
The three time points following CAR-DC cell therapy: Month 1, Month 3, and Month 6.4
The difference between the 6-minute walk test result and the baseline value before treatment
Time frame
The three time points following CAR-DC cell therapy: Month 1, Month 3, and Month 6.Locations
Sponsors and contacts
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Source ClinicalTrials.gov
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