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

Safety and Efficacy of Allogeneic Immunosuppressive CAR-DC Targeting FAP in the Treatment of Acute Myocardial Infarction With Cardiogenic Shock

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiogenic Shock; STEMI - ST Elevation Myocardial Infarction; Cardiogenic Shock Post Myocardial Infarction
• Intervention / Treatment: Biological: FAP allogeneic immunosuppressive CAR-DC

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• 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
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Xinyang Hu; Phone Number: 86-0571-87783777; Email: hxy0507@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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.

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 allogeneic FAP iCDC; 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.; 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.; 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).; 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.	Biological: FAP allogeneic immunosuppressive CAR-DC; Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion at the first day of shock.
No Intervention: Standard therapy; Patients in the control group do not receive cellular therapy intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of iCDC treatment-emergent adverse events	in 14 days after injection
The proportion of subjects with Dose-limiting toxicity (DLT)	The proportion of participants with DLT as assessed by CTCAE v5.0	in 14 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality at 30 days after iCDC treatment	30 days after injection
Systolic blood pressure	Systolic blood pressure (mmHg) measured using a calibrated sphygmomanometer under standardized conditions.	24 hours、48 hours、72 hours、7 days after injection
Diastolic blood pressure	Diastolic blood pressure (mmHg) measured using a calibrated sphygmomanometer under standardized conditions.	24 hours、48 hours、72 hours、7 days after injection
Mean arterial pressure	The mean arterial pressure (MAP) is calculated using the following formula: MAP=DBP+1/3(SBP-DBP)；DBP : Diastolic blood pressure，SBP ：Systolic blood pressure	24 hours、48 hours、72 hours、7 days after injection
Time to hemodynamic stability	Sustained (> 60 min) systolic blood pressure >90 mmHg without requirement for catecholamines and without signs of peripheral endorgan hypoperfusion	From the end of the iCDC infusion to achievement of hemodynamic stability, assessed continuously until ICU discharge (up to 30 days).
Dose of vasopressors	Dose of vasopressors administered to the participant.	24 hours、48 hours、72 hours、7 days after injection
Duration of vasopressor use	Duration of vasopressor therapy in days treated with vasopressor between enrollment and hospital discharge. A day treated with vasopressor is any day during the hospital period where the patient received a vasopressor.	From enrollment to hospital discharge (up to 30 days).
Dose of inotropic drugs	Dose of inotropic drugs administered to the participant.	24 hours、48 hours、72 hours、7 days after injection
Duration of inotropic drugs use	Duration of inotropic drugs therapy in days treated with inotropic drugs between enrollment and hospital discharge. A day treated with inotropic drugs is any day during the hospital period where the patient received inotropic drugs	From enrollment to hospital discharge (up to 30 days).
Serum lactate level	Lactate is assessed via arterial blood gas analysis.	The measurement frequency is once every 8 hours for a duration of 48 hours.
Change in B-type natriuretic peptide (BNP) level from baseline	Change in serum B-type natriuretic peptide concentration compared with baseline.	7 days，14 days，30 days after injection.
Change in C-reactive protein (CRP) level from baseline	Change in serum C-reactive protein concentration compared with baseline.	24 hours, 72 hours, 7 days，14 days after injection.
Change in serum creatinine level from baseline	Change in serum creatinine concentration compared with baseline.	24 hours, 72 hours, 7 days，14 days after injection.
Change in ALT (Alanine Aminotransferase) level from baseline	Change in serum ALT concentration compared with baseline.	24 hours, 72 hours, 7 days，14 days after injection.
Change in AST (Aspartate Aminotransferase) level from baseline	Change in serum AST concentration compared with baseline.	24 hours, 72 hours, 7 days，14 days after injection.
Change in Interleukin-6 (IL-6) levels from baseline	Change in serum Interleukin-6 (IL-6) levels compared with baseline.	24 hours, 72 hours, 7 days，14 days after injection.
Need for mechanical ventilation	Need for mechanical ventilation is defined as requiring invasive or non-invasive positive pressure ventilation for at least 1 hour due to respiratory failure.	From the end of the drug infusion until ICU discharge (up to 30 days).
Duration of mechanical ventilation	Duration of mechanical ventilation is defined as the total number of hours from the initiation of invasive or non-invasive ventilation until the last successful extubation	From the initiation of mechanical ventilation until ICU discharge (up to 30 days).
Requirement for left ventricular assist device implantation	Requirement for left ventricular assist device implantation is defined as the need for implantation of a left ventricular assist device as bridge-to-transplant or destination therapy in patients with cardiogenic shock or end-stage heart failure who fail to maintain adequate end-organ perfusion despite optimized medical therapy.	From the end of iCDC infusion through study completion (up to 30 days).
Duration of left ventricular assist device use	Duration of left ventricular assist device use is defined as the total time from completion of device implantation until device removal, patient death, or the study cutoff date, whichever occurs first.	From left ventricular assist device implantation through study completion (up to 30 days).
Simplified Acute Physiology Score II	The Simplified Acute Physiology Score II (SAPS II) is a validated severity-of-disease scoring system used to assess the physiological status of critically ill patients. The score ranges from 0 to 163, with higher scores indicating greater disease severity and a worse prognosis. SAPS II will be calculated based on the worst physiological values recorded during each 24-hour period.	Daily from ICU admission through ICU discharge (up to 30 days).
time to recovery from cardiogenic shock	Time to recovery from cardiogenic shock is defined as the duration from the end of the single study drug infusion to the achievement of predefined criteria for hemodynamic stability and improvement in end-organ perfusion.	From the end of iCDC infusion to recovery from cardiogenic shock, assessed continuously until ICU discharge (up to 30 days).
length of stay at the intensive care unit	Length of stay in the ICU is defined as the total time from ICU admission until ICU discharge.	From ICU admission until ICU discharge (up to 30 days).
Length of hospital stay;	Total hospital length of stay is defined as the total calendar days from patient admission registration until final discharge or death, whichever occurs first.	From hospital admission until hospital discharge or death (up to 30 days).
Left ventricular ejection fraction (LVEF)	The difference of LVEF from baseline. LVEF will be assessed by echo.	1 month after injection
SCAI Shock Classification	The SCAI shock classification is a standardized, five-stage system (from A to E) used to categorize the severity of cardiogenic shock based on clinical, hemodynamic, and biomarker criteria.	3 days、7 days、14 days after injection
assessment of heart failure symptom	The difference of heart failure symptom, which will be assessed by NYHA grading and KCCQ score.	1 month after injection
Incidence of major adverse cardiovascular events (MACE)	Incidence of Cardiac death, readmission due to heart failure.	1 month after injection
incidence of adverse events	Incidence of adverse events of heart, nerve system, mental system, digestive system and immune system.	From the end of the drug infusion through study completion，up to 30 days.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Xinyang Hu, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2026
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: acute myocardial infarction with cardiogenic shock
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction; Shock, Cardiogenic
• Other Study ID Numbers: YAN2025-1716

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