Safety and Efficacy of FAP iCDC in Ischemic Cardiomyopathy

Safety and Efficacy of FAP-Targeted Immunosuppressive CAR-DC in the Treatment of Ischemic Cardiomyopathy

This study aims to evaluate the safety and efficacy of fibroblast activation protein (FAP)-targeted autologous immunosuppressive chimeric antigen receptor dendritic cell (iCDC) therapy in patients with ischemic cardiomyopathy, and to explore its potential as a novel therapeutic strategy for this disease.

Study Overview

• Status: Recruiting
• Conditions: Cell Therapy; Ischemic Cardiomyopathy
• Intervention / Treatment: Biological: autologus FAP-targeted immunosuppressive CAR-DCs (iCDC); Other: Standard medical treatment

Detailed Description

Ischemic heart disease (IHD) is becoming an increasingly serious global public health challenge due to its rising prevalence and the continuous increase in human life expectancy. Despite substantial advances in reperfusion therapy, pharmacological treatment, and risk factor management in recent decades, clinical prognosis remains poor. Many patients continue to experience adverse cardiac remodeling after the initial ischemic injury and eventually progress to heart failure. This persistent residual risk suggests that current therapeutic strategies do not fully address key pathogenic mechanisms underlying disease progression. Inflammation plays a central role in linking acute myocardial injury to chronic cardiac remodeling.

Dendritic cells (DCs), as professional antigen-presenting cells, function at the interface between innate and adaptive immunity and play a critical role in coordinating immune responses within the tissue microenvironment. Recent advances in the study of tolerogenic dendritic cells (tolerogenic DCs) have provided new insights into their potential application in cardiovascular diseases. Unlike conventional immunostimulatory DCs, tolerogenic DCs can induce antigen-specific immune tolerance through multiple mechanisms, including secretion of regulatory cytokines, expression of co-inhibitory ligands, suppression of effector T-cell responses, and induction of regulatory T cells. These properties make DCs a promising but underexplored platform for immune modulation.

This study evaluates a novel therapeutic strategy using fibroblast activation protein (FAP)-targeted autologous immunosuppressive chimeric antigen receptor dendritic cell (CAR-DC) therapy, also referred to as iCDC therapy, in patients with ischemic cardiomyopathy. This approach is designed to direct engineered dendritic cells to sites of cardiac injury and fibrosis, with the goal of modulating the balance between injurious and reparative immune responses. By targeting local immune regulation at the site of injury, this strategy may help attenuate adverse cardiac remodeling while potentially avoiding the systemic immunosuppression associated with conventional therapies.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiamin Li, MD; Phone Number: 86-18868112006; Email: 21818216@zju.edu.cn

Study Locations

• China
  • Zhejiang / 浙江
    • Hangzhou, Zhejiang / 浙江, China, 310009
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Jiamin Li, Dr; Phone Number: 18868112006; Email: 21818216@zju.edu.cn
      • Contact: Email: 21818216@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years and ≤75 years.
• Diagnosis of ischemic cardiomyopathy, with at least 3 months of optimized guideline-directed medical therapy (GDMT) at maximally tolerated doses; left ventricular ejection fraction (LVEF) <35%; New York Heart Association (NYHA) functional class III-IV.
• Ability to understand the risks, benefits, and treatment alternatives of immunoregulatory CAR-DC therapy, and willingness to participate in the study; the patient or his/her legally authorized representative must provide written informed consent prior to study enrollment.
• Adequate hematologic function defined as: hematocrit >30%, lymphocyte count >0.5 × 10⁹/L, and platelet count >60 × 10⁹/L.

Exclusion Criteria:

• Life expectancy <1 year due to non-cardiac conditions.

Cardiac resynchronization therapy (CRT) implantation within 3 months prior to enrollment or planned CRT implantation.

Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to enrollment OR plan to PCI.

Presence of non-ischemic cardiomyopathy, including but not limited to dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic cardiomyopathy, peripartum cardiomyopathy, inflammatory or immune-mediated cardiomyopathy, metabolic or genetic cardiomyopathy, or cardiomyopathy secondary to moderate-to-severe valvular heart disease, congenital heart disease, or other non-ischemic etiologies.

Persistent hemodynamic instability.

End-stage renal disease (eGFR <25 mL/min/1.73 m²) requiring or receiving renal replacement therapy (hemodialysis or peritoneal dialysis).

Active autoimmune disease requiring immunosuppressive therapy.

History of malignancy.

Active infection, including but not limited to active hepatitis B (HBV DNA >1000 copies/mL by PCR), hepatitis C, syphilis, or human immunodeficiency virus (HIV) infection, or uncontrolled systemic fungal, bacterial, viral, or other infections.

Pregnant women.

Known contraindications to the investigational product or study-related procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of autologus FAP iCDC; Administration of FAP immunosuppressive CAR-DC cell therapy in ischemic cardiomyopathy. Patients are planned to be enrolled in the dose-escalation trial (1×10^5/kg、4×10^5/kg、and 8×10^5/kg) .The first dose group (4×10⁵/kg) initially enrolls 3 subjects to observe Dose-Limiting Toxicity (DLT) responses. （1）If no DLT occurs and all 3 subjects demonstrate efficacy after 6 months of treatment, and this dose is determined as the safe and effective dose. （2）If 1 subject experiences DLT, 3 additional subjects are enrolled. ·If 1/6 subjects develops DLT, and efficacy is not fully achieved in all 6 subjects, escalate to the next dose group (8×10^5/kg). ·If ≥2/6 subjects develop DLT, de-escalate to the previous dose group (1×10^5/kg). （3）After identifying a safe and effective dose, enrollment will be expanded at this dose to bring the total sample size to 15 subjects, to further evaluate safety and efficacy.	Biological: autologus FAP-targeted immunosuppressive CAR-DCs (iCDC); Each subject receives FAP-targeted immunosuppressive CAR-DCs by intravenous infusion after enrollment.
Active Comparator: Standard treatment control; Participants in this arm will receive standard medical treatment for ischemic cardiomyopathy according to current clinical practice and guideline-directed medical therapy. These participants will not receive iCDC therapy but will undergo scheduled follow-up assessments for safety and efficacy comparisons.	Other: Standard medical treatment; Participants receive standard medical treatment for ischemic cardiomyopathy according to current clinical practice and guideline-directed medical therapy. No iCDC therapy is administered in this arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLT)	Incidence of dose-limiting toxicities (DLT) within 14 days after administration of FAP-targeted immunoregulatory CAR-DC therapy	Within 14 days after treatment
Incidence of Treatment-Emergent Adverse Events (TEAE)	Incidence of treatment-emergent adverse events (TEAE) occurring within 6 months after treatment in patients with ischemic cardiomyopathy.	Within 6 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Ventricular Ejection Fraction (LVEF) by Echocardiography	Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, 6 months
Change in left ventricular end-systolic volume (LVESV) as assessed by Echocardiography	Change from baseline in left ventricular end-systolic volume (LVESV)measured by echocardiography, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in left ventricular end-diastolic volume (LVEDV) by Echocardiography	Change from baseline in left ventricular end-diastolic volume (LVEDV) measured by echocardiography, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in global longitudinal strain (GLS) measured by Echocardiography	Change from baseline in global longitudinal strain (GLS) measured by echocardiography, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, 6 months
Change in wall motion score index (WMSI) measured by Echocardiography	Change from baseline in wall motion score index (WMSI) measured by echocardiography, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, 6 months
Change in left ventricular ejection fraction (LVEF) by Cardiac Magnetic Resonance Imaging	Change from baseline in left ventricular ejection fraction (LVEF) measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 6 months
Change in left ventricular end-systolic volume (LVESV) by Cardiac Magnetic Resonance Imaging	Change from baseline in left ventricular end-systolic volume (LVESV) measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Change in left ventricular end-diastolic volume (LVEDV) by Cardiac Magnetic Resonance Imaging	Change from baseline in left ventricular end-diastolic volume (LVEDV) measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 6 months
Change in stroke volume (SV) by Cardiac Magnetic Resonance Imaging	Change from baseline in stroke volume (SV) measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Change in Myocardial Late Gadolinium Enhancement Volume by Cardiac Magnetic Resonance Imaging	Change from baseline in myocardial late gadolinium enhancement (LGE) volume percentage measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Change in Extracellular Volume Fraction in Remote Myocardium by Cardiac Magnetic Resonance Imaging	Change from baseline in extracellular volume fraction (ECV) in remote myocardium measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Change in Myocardial Scar Transmurality by Cardiac Magnetic Resonance Imaging	Change from baseline in myocardial scar transmurality percentage measured by cardiac magnetic resonance imaging, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Change in Serum B-type Natriuretic Peptide (BNP) Level	Change from baseline in serum B-type natriuretic peptide (BNP) level, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in Six-Minute Walk Test Distance	Change from baseline in six-minute walk test distance, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in Heart Failure Symptom Assessments--NYHA	Change from baseline in heart failure symptom and functional status assessments, including New York Heart Association (NYHA) functional class, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in Heart Failure Symptom Assessments--INTERMACS	Change from baseline in heart failure symptom and functional status assessments, including INTERMACS profile, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in Heart Functional Status Assessments-KCCQ	Change from baseline in heart failure symptom and functional status assessments, including Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline, 3 months, and 6 months
Change in Cardiac 18F-FAPI Uptake by PET/CT	Change from baseline in cardiac 18F-FAPI maximum standardized uptake value (SUVmax) measured by positron emission tomography/computed tomography (PET/CT), and between-group difference between the iCDC treatment group and the standard treatment control group.	Baseline and 6 months
Incidence of Major Adverse Cardiovascular Events	Incidence of major adverse cardiovascular events (MACE), including all-cause death, hospitalization for heart failure, myocardial infarction, and stroke, in the iCDC treatment group and the standard treatment control group.	Up to 6 months
Incidence of Adverse Events	Incidence of adverse events in the iCDC treatment group and the standard treatment control group. Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events, version 5.0.	Up to 6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ischemic cardiomyopathy; dendritic cell; immune tolerance
• Other Study ID Numbers: YAN2026-0257

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No