Safety and Efficacy of FAP iCDC in Acute Myocardial Infarction With Cardiogenic Shock

Zhejiang University

Status and phase: Not yet enrolling; Phase 1

Conditions: Cardiogenic Shock Post Myocardial Infarction; STEMI - ST Elevation Myocardial Infarction; Cardiogenic Shock

Treatments: Biological: FAP allogeneic immunosuppressive CAR-DC

Study type: Interventional

Funder types: Other

Identifiers

NCT07380659

YAN2025-1716

Details and patient eligibility

About

To study the safety and efficacy of fibroblast activation protein (FAP)-targeted allogeneic immunosuppressive chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of acute myocardial infarction with cardiogenic shock and provide a new method for the treatment of acute myocardial infarction with cardiogenic shock.

Full description

Background: Cardiogenic shock following acute myocardial infarction (AMI) remains a major unresolved clinical challenge. Despite advances in urgent revascularization and mechanical circulatory support, short-term mortality remains unacceptably high, approaching 40% within 30 days. Few evidence-based therapies have demonstrated a meaningful survival benefit, highlighting the urgent need for novel, mechanism-driven interventions. Growing clinical and experimental evidence indicates that a dysregulated systemic inflammatory response-manifested by hyperthermia, leukocytosis, and elevated proinflammatory mediators-plays a central role in the pathophysiology and progression of cardiogenic shock. Excessive inflammation exacerbates myocardial dysfunction, promotes multiorgan injury, and impairs recovery, suggesting that targeted immunomodulation may represent a complementary therapeutic strategy in this high-risk population. Dendritic cells (DCs), as professional antigen-presenting cells, occupy a pivotal position at the interface of innate and adaptive immunity and are uniquely suited to orchestrate context-dependent immune responses. In particular, tolerogenic DCs exert potent immunosuppressive effects through regulatory cytokine production, expression of co-inhibitory ligands, antigen-specific suppression of effector T cells, and induction of regulatory T cells. Collectively, these properties render DCs an attractive yet underexplored cellular platform for resolving excessive inflammation and promoting tissue repair in cardiogenic shock with AMI.

Purpose: In this prospective clinical study, the investigators engineered a stable, immunosuppressive, and fibrotic lesion-targeted DC therapy, termed immunosuppressive DCs (iCDC). This study was designed to evaluate the safety and preliminary efficacy of allogeneic fibroblast activation protein (FAP)-targeted iCDC therapy in patients with AMI complicated by cardiogenic shock.

Study design: This single-center, prospective, concurrent non-randomized controlled clinical trial enrolls patients aged 18-80 years presenting with acute myocardial infarction complicated by cardiogenic shock. Eligible patients are treated with allogeneic FAP-targeted immunosuppressive iCDC therapy.

Outcome measure: The primary outcome is the safety of FAP-targeted immunosuppressive iCDC therapy in patients with AMI complicated by cardiogenic shock. Secondary outcomes include 30-day all-cause mortality; hemodynamic parameters following iCDC therapy (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate); time to hemodynamic stabilization; dose and duration of vasopressor and inotropic support; arterial lactate levels; changes in biomarkers (BNP, CRP, creatinine, ALT, AST, and inflammatory mediators); need for and duration of mechanical ventilation; need for and duration of left ventricular assist device implantation; intensive care unit and total hospital length of stay; left ventricular ejection fraction assessed by echocardiography; SAPS II score; SCAI shock classification; heart failure symptom burden assessed by NYHA functional class and the Kansas City Cardiomyopathy Questionnaire; incidence of major adverse cardiovascular events (MACE), including cardiac death and heart failure hospitalization; and incidence of adverse events.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria（patients）:

• Age ≥ 18 years and < 80 years.

• Acute ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock, meeting all the following conditions:

  1. Post-emergent revascularization (PCI or CABG)

  2. Systolic blood pressure < 90 mmHg for >30 minutes, or requiring catecholamine support to maintain systolic blood pressure >90 mmHg

  3. Signs of impaired organ perfusion, meeting at least one of the following criteria:

     1. Altered mental status
     2. Cold, clammy skin and extremities
     3. Oliguria, with urine output <30 mL/h
     4. Arterial lactate level >2 mmol/L

• The patient or their legally authorized representative is capable of providing verbal confirmation of understanding the trial risks, benefits, and treatment alternatives associated with receiving immunosuppressive CAR-DC therapy, and provides written informed consent prior to participation in this clinical trial.

Exclusion Criteria（patients）:

1. Acute mechanical complications of infarction (e.g., ventricular septal rupture, acute mitral regurgitation).

2. Cardiac arrest.

3. Hypoxic-ischemic brain injury (cerebral injury with fixed and dilated pupils not attributable to medication).

4. Shock due to other causes (e.g., sepsis, hypovolemia).

5. Resuscitation duration >30 minutes.

6. Absence of spontaneous cardiac activity.

7. Persistent electrical instability.

8. Active bleeding or contraindications to heparin use.

9. Active autoimmune disease requiring immunosuppressive therapy.

10. History of malignancy.

11. Infection, including:

    • Active hepatitis B (HBV DNA >1000 copies/mL by PCR), hepatitis C, syphilis, or HIV infection at screening.
    • Uncontrolled systemic fungal, bacterial, viral, or other pathogen infections.

12. Pregnant women.

13. Contraindications to the investigational drug or study procedures.

Inclusion Criteria（donors）:

• Age ≥ 18 years and ≤ 75 years.
• Has provided written informed consent.
• Hematocrit >30%, lymphocyte count >0.5 × 10^9/L, platelet count >60 × 10^9/L.
• Pathogen screening results must be negative for HIV (antigen, core antibody, and RNA), HBV (surface antigen and core antibody), HCV, syphilis, CMV, and EBV.

Exclusion Criteria（donors）:

• Active infection requiring treatment.
• History of malignancy.
• Active autoimmune disease requiring immunosuppressive therapy.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 2 patient groups

Administration of allogeneic FAP iCDC

Experimental group

Description:

Administration of FAP immunosuppressive CAR-DC cell therapy in AMI CS. 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 8-10 subjects, to further evaluate safety and efficacy.

Treatment:

Biological: FAP allogeneic immunosuppressive CAR-DC

Standard therapy

No Intervention group

Description:

Patients in the control group do not receive cellular therapy intervention.