Safety and Efficacy of FAP iCDC in Ischemia Cardiomyopathy

Safety and Efficacy of Immunosuppressive CAR-DC Targeting FAP in the Treatment of Ischemia Cardiomyopathy

To study the safety and efficacy of fibroblast activation protein (FAP)-targeted autologus immunosuppressive chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of ischemic cardiomyopathy, aiming to provide a novel therapeutic strategy for the disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Cell Therapy; Ischemic Cardiomyopathy
• Intervention / Treatment: Biological: autologus FAP-targeted immunosuppressive CAR-DCs (iCDC)

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, the clinical prognosis remains poor. A large proportion of patients continue to experience adverse cardiac remodeling after the initial ischemic injury, eventually progressing to heart failure. This persistent "residual risk" suggests that current therapeutic strategies do not fully address key pathogenic mechanisms underlying disease progression. In particular, 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 the secretion of regulatory cytokines, expression of co-inhibitory ligands, suppression of effector T-cell responses in an antigen-specific manner, and induction of regulatory T cells. These properties make DCs a promising yet underexplored platform for immune modulation.

Based on this concept, we have developed a novel therapeutic strategy using engineered dendritic cells with immunoregulatory and lesion-targeting properties, termed immunoregulatory and lesion-targeted dendritic cells (iCDC). This approach aims to deliver engineered DCs to sites of cardiac injury, thereby 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): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiamin Li, MD; Phone Number: 86-18868112006; 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.

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 <15 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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.

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 left ventricular ejection fraction (LVEF) measured by echocardiography at 3, 6, and 12 months after iCDC treatment.	Baseline, 3 months, 6 months, and 12 months
Change in Left Ventricular Ejection Fraction as assessed by Cardiac MRI	Change in Left Ventricular Ejection Fraction measured by Cardiac MRI	Baseline, 6 months, and 12 months
Change in Myocardial Late Gadolinium Enhancement Volume by CMR	Change from baseline myocardial late gadolinium enhancement volume percentage measured by cardiac MRI at 6 and 12 months.	Baseline, 6 months, and 12 months
Change in left ventricular end-systolic diameter measured by Echocardiography	Change from baseline left ventricular end-systolic diameter measured by echocardiography.	Baseline, 3 months, 6 months, and 12 months
Change in left ventricular end-diastolic diameter measured by Echocardiography	Change from baseline left ventricular end-diastolic diametermeasured by echocardiography.	Baseline, 3 months, 6 months, and 12 months
Change in Left Ventricular end-systolic Volume by Echocardiography	Change from baseline left ventricular end-systolic volume (LVESV) measured by echocardiography.	Baseline, 3 months, 6 months, and 12 months
Change in Left Ventricular end-diastolic Volume by Echocardiography	Change from baseline left ventricular end-diastolic volume (LVEDV) measured by echocardiography.	Baseline, 3 months, 6 months, and 12 months
Change in Left Ventricular end-systolic Volume by Cardiac MRI	Change from baseline left ventricular end-systolic volume (LVESV) measured by cardiac MRI.	Baseline, 6 months, and 12 months
Change in Left Ventricular end-diastolic Volume by Cardiac MRI	Change from baseline left ventricular end-diastolic volume (LVEDV) measured by cardiac MRI.	Baseline, 6 months, and 12 months
Change in Rest MBF by PET/CT	Change from baseline myocardial blood flow parameters measured by PET/CT, including resting myocardial blood flow (Rest MBF)	Baseline, 6 months, and 12 months
Change in Stress MBF by PET/CT	Change from baseline myocardial blood flow parameters measured by PET/CT, including stress myocardial blood flow (Stress MBF)	Baseline, 6 months, and 12 months
Change in MFR by PET/CT	Change from baseline myocardial blood flow parameters measured by PET/CT, myocardial flow reserve (MFR).	Baseline, 6 months, and 12 months
Change in Coronary Plaque Burden	Coronary plaque burden assessed by percent atheroma volume (PAV) measured by coronary CT angiography.	12 months after treatment
Change in Stability by Coronary CTA	Plaque stability assessed by fibrous cap thickness (FCT) measured by coronary CT angiography.	12 months after treatment
Change in ALT	Changes in laboratory biomarkers including ALT following iCDC treatment.	3 days, 7 days, 14 days, 1 month, 3 months, 6 months, and 12 months
Change in AST	Changes in laboratory biomarkers including AST	3 days, 7 days, 14 days, 1 month, 3 months, 6 months, and 12 months
Change in creatinine	Changes in laboratory biomarkers including creatinine following iCDC treatment.	3 days, 7 days, 14 days, 1 month, 3 months, 6 months, and 12 months
Change in CRP	Changes in laboratory biomarkers including CRP following iCDC treatment.	3 days, 7 days, 14 days, 1 month, 3 months, 6 months, and 12 months
Change in inflammatory cytokines	Changes in laboratory biomarkers including inflammatory cytokines following iCDC treatment.	3 days, 7 days, 14 days, 1 month, 3 months, 6 months, and 12 months
Change in BNP Level	Change from baseline serum BNP levels following iCDC treatment.	Baseline, 3 months, 6 months, and 12 months
Change in 6-Minute Walk Distance	Change from baseline functional exercise capacity assessed by the 6-minute walk test.	Baseline, 3 months, 6 months, and 12 months
Change in NYHA	Change from baseline heart failure symptoms assessed by NYHA functional class.	Baseline, 3 months, 6 months, and 12 months
Change in KCCQ	Change from baseline heart failure symptoms assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ).	Baseline, 3 months, 6 months, and 12 months
Incidence of Major Adverse Cardiovascular Events (MACE)	Incidence of major adverse cardiovascular events including all-cause death and hospitalization for heart failure.	12 months
Incidence of Adverse Events	Incidence of adverse events following iCDC treatment.	Up to 12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 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): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 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