Safety and Feasibility of CIK Cell Therapy in HCC After Tumor Resection

Safety and Feasibility of Autologous Cytokine Induced Killer (CIK) Cells Infusion as an Adjuvant Therapy in Post Resection Hepatocellular Carcinoma (HCC) Patients

This study tests whether it is safe and feasible to give patients with hepatocellular carcinoma (liver cancer) an infusion of their own (autologous) immune cells, called cytokine-induced killer (CIK) cells, after they have had surgery to remove their liver tumor. The patient's own blood cells are collected and grown in a laboratory to create the CIK cells, which are then given back to the patient through six intravenous infusions over about two months. Patients are followed for six months to check for side effects and early signs of whether the cancer returns.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Biological: Autologous Cytokine-Induced Killer (CIK) Cells

Detailed Description

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related mortality worldwide. Even after curative-intent surgical resection, disease recurrence occurs in approximately 60-70% of patients within five years, and no adjuvant systemic therapy has demonstrated a consistent recurrence-free survival or overall survival benefit in this setting. Cytokine-induced killer (CIK) cells are ex vivo-expanded autologous immune effector cells with a heterogeneous phenotype dominated by CD3⁺CD56⁺ cells, combining T-cell and NK-cell features and exhibiting MHC-unrestricted cytotoxicity against tumor cells. Phase II/III trials and subsequent meta-analyses conducted predominantly in East Asian populations have reported improved recurrence-free and overall survival with adjuvant CIK therapy following HCC resection, without a corresponding increase in severe (Grade ≥3) adverse events, and the South Korean Ministry of Food and Drug Safety approved a CIK-based product (Immuncell-LC) on this basis in 2022. No clinical data exist to date for an Iranian population, which differs from East Asian cohorts in HCC etiology (notably HBV prevalence and metabolic-associated steatotic liver disease burden) and genetic background.

This is a single-center, open-label, single-arm, phase I safety and feasibility study conducted at the Liver Transplant and Surgery Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, in collaboration with Royan Institute. Full eligibility criteria are listed in the Eligibility section of this record.

For each patient, peripheral blood mononuclear cells (PBMCs) are isolated and expanded ex vivo under Good Manufacturing Practice (GMP) conditions for 14-21 days using IFN-γ, anti-CD3 antibody, and IL-2 to generate the autologous CIK cell product. Prior to release, each batch undergoes quality control testing for viability, CD3⁺CD56⁺ phenotype, antitumor cytotoxicity, sterility, and endotoxin level against pre-specified thresholds (≥85% viability, ≥60% CD3⁺CD56⁺, ≥30% cytotoxicity, endotoxin ≤5 EU/kg, negative microbial/mycoplasma testing); only batches meeting these criteria are released for infusion.

Each patient receives six intravenous infusions of autologous CIK cells administered as a slow infusion over approximately 60 minutes under sterile conditions: three weekly infusions (weeks 0, 1, and 2) followed by three biweekly infusions (weeks 4, 6, and 8). Vital signs are monitored before, during, and for two hours after each infusion. No routine premedication is given; mild fever is managed with acetaminophen. Adverse event monitoring and grading methodology are detailed under Outcome Measures. Over the 6-month follow-up period, scheduled assessments also include laboratory testing (including AFP, PIVKA-II, liver function and coagulation panels), peripheral blood lymphocyte immunophenotyping (CD56⁺CD16⁺CD3-, CD3⁺CD8⁺, CD3⁺CD56⁺CD16⁺, CD3⁺CD4⁺ populations at month 6 versus baseline), and contrast-enhanced MRI at months 3 and 6. Given the phase I descriptive design and small sample size, statistical analysis is planned to be descriptive rather than inferential.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Massoud Vosough, MD, Ph.D.; Phone Number: 98 21 2251 8388; Email: masvos@yahoo.com

Study Locations

• Iran
  • Tehran Province
    • Tehran, Tehran Province, Iran
      • Liver Transplant and Surgery Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences
      • Contact: Mohsen Nassiri-Toosi, MD; Phone Number: +98 21 6119 2996; Email: nasirimohsen@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age between 18 and 80 years
• Documented HCC at BCLC stage 0-A, having undergone surgical tumor resection
• Single tumor or ≤3 nodules, each ≤3 cm
• Child-Pugh score A-B
• ECOG performance status 0-1
• Confirmed cancer-free status one month after surgery
• Written informed consent
• Leukocyte count > 3 × 10⁹/L
• Absolute neutrophil count (ANC) ≥ 1,000/µL
• Hemoglobin ≥ 8.5 g/dL
• Platelet count > 50 × 10⁹/L
• BUN and serum creatinine ≤ 1.5 × upper limit of normal No extrahepatic abdominal disease spread, confirmed by abdominal CT/MRI

Exclusion Criteria:

• Active infection or uncontrolled viremia (particularly HBV, HCV, or HIV)
• Any cell therapy or immunotherapy in the past 6 months, or current participation in another clinical study
• Another malignancy (prior or concurrent) differing from HCC in primary site or histology
• Clinically significant cardiovascular disease (e.g., heart failure, serious arrhythmia, symptomatic coronary artery disease)
• History of organ transplantation
• Primary or secondary immunodeficiency, or active autoimmune disease
• Severe allergic disorder or history of anaphylaxis
• Pregnancy or breastfeeding at study entry
• Women of childbearing potential intending to become pregnant

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: CIK Cell Adjuvant Therapy; Patients with HCC who have undergone curative surgical resection receive six intravenous infusions of autologous CIK cells (three weekly, three biweekly) in addition to standard postoperative care.	Biological: Autologous Cytokine-Induced Killer (CIK) Cells; PBMCs are collected from the patient, expanded ex vivo for 14-21 days under GMP conditions administered as 6 intravenous infusions (weeks 0, 1, 2, then weeks 4, 6, 8) following release testing for sterility, viability, and phenotype.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events following CIK cell infusion	Frequency, type, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs), graded per CTCAE v5.0.	From first infusion through 6 months post-treatment (assessed at weeks 1-10 and months 3 and 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival (RFS)	Time from study enrollment to first tumor recurrence (intrahepatic or extrahepatic) or death from any cause, whichever occurs first.	From date of enrollment until first documented intrahepatic or extrahepatic tumor recurrence, or death from any cause, whichever occurs first, assessed up to 6 months
Overall Survival (OS)	Time from study enrollment to death from any cause.	From date of enrollment until death from any cause, assessed up to 6 months

Collaborators and Investigators

• Sponsor: Royan Institute
• Collaborators: Kian Immune Cell Company; Bahar Tashkhis Teb
• Investigators: Study Director: Massoud Vosough, MD, Ph.D., Royan Institute; Principal Investigator: Mohsen Nassiri-Toosi, MD, Liver Transplant Research Center, Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; Adjuvant therapy; CIK Cells; Cytokine-induced killer cell; HCC recurrence; HCC resection
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Cell Physiological Phenomena; Cell Count
• Other Study ID Numbers: 404000269; IRCT20201229049871N1 (Registry Identifier: Iranian Registry of Clinical Trials (IRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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