Overview
Primary Outcomes The primary objective of this trial is to test the safety of formulations containing dendritic cells (DCs) and natural killer (NK) cells cultured in vitro. By evaluating the reactions following the administration of autologous dendritic cells via axillary lymph node injection and natural killer cells via intravenous injection, the study aims to determine the safety profile of these trial products for human use.
Secondary Outcomes
To verify the success rate of the cultured cell formulations and assess the cytotoxic capacity of natural killer cells in targeting and killing tumor cells. The evaluation of these secondary objectives involves analyzing specific subcategories, which can be divided into two major components:
- Validation of Cultured Cell Preparation Success: Assessing the proliferation rate, recovery rate, survival rate, and tumor-killing capacity of the cultured autologous dendritic cells and natural killer cells.
- Validation of Antitumor Effectiveness: Evaluating the antitumor efficacy of the trial products administered via axillary lymph node injection of autologous dendritic cells and intravenous infusion of autologous natural killer cells.
Description
Research Background and Current Status of Medical Technology According to data from the Ministry of Health, cancer has consistently ranked as the leading cause of death in Taiwan. Although various treatments for cancer, including surgery, chemotherapy, and radiotherapy, are currently available, there is still significant room for improvement in terms of extending survival and reducing side effects. Recently, research on natural killer (NK) cell therapy has gained attention both domestically and internationally. While the therapeutic effects remain uncertain and most countries are still in the clinical trial stage, preliminary results and studies from other countries suggest that combining NK cell therapy with traditional treatments like chemotherapy or radiotherapy may provide additional benefits for cancer patients.
Natural killer cells are among the first-line innate immune defenses in the human body and are considered one of the most potent and effective cells for combating cancer and viral infections. Compared to other anti-cancer immune cells, such as cytotoxic T cells or dendritic cells, NK cells exhibit stronger cytotoxicity, a broader spectrum of activity, and are not restricted by tissue compatibility antigens. They can directly attack cancer cells without the need for prior sensitization. Since the discovery of NK cells in the 1970s, immunologists have hypothesized that expanding NK cells in large quantities and reinfusing them into patients could achieve anti-cancer effects, enhance immune regulation, and improve overall immunity. This forms the theoretical basis of NK cell therapy.
In simple terms, NK cell therapy involves the use of cell culture techniques to rapidly proliferate a patient's NK cells in vitro and then reinject them into the patient. This approach aims to boost the patient's innate anti-cancer capacity and support conventional therapies in achieving cancer treatment goals.
Laboratory studies using animal models and in vitro experiments have highlighted several theoretical advantages of NK cell therapy for cancer treatment:
- NK cells exhibit the strongest anti-cancer activity in the human body, directly killing cancer cells and inhibiting tumor growth and spread.
- NK cells suppress the formation of new blood vessels around tumors, restricting the supply of nutrients necessary for tumor growth.
Although the clinical effectiveness of NK cell therapy for cancer in humans has yet to be confirmed, some preliminary international studies suggest that adding activated NK cells or cytokine-induced killer (CIK) cells to standard treatments may help inhibit the spread of cancer cells and slow disease progression.
Characteristics of Human Cell Therapy Products and Usage Experience
- Cell Source and Characteristics Source: Autologous cells
- Characteristics
Dendritic cells (DCs) have the ability to activate adaptive immune functions. NK cells possess tumor-killing capabilities.
Rationale for Use in This Indication:
Preliminary clinical studies indicate that in non-small cell lung cancer (NSCLC) patients, groups receiving NK cell (or NK + DC) immunotherapy in addition to traditional treatments (surgery, chemotherapy, or radiotherapy) showed better outcomes in individual trials compared to control groups that received only traditional treatments. These outcomes included improved objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and, in some cases, enhanced quality of life (refer to the summary table on the next page for details).
2. Usage Experience Numerous clinical trials have already been conducted internationally. The investigational drug in this trial is being tested in humans for the first time.
Eligibility
Inclusion Criteria:
- Eligibility of Participants:
- Diagnosed histologically or cytologically with stage IIIB or stage IV non-small
cell lung cancer (NSCLC) or patients with recurrence or progression following
multimodal treatments (radiotherapy, surgical resection, or therapeutic
chemoradiotherapy for locally advanced disease).
- Have undergone at least two systemic therapies for advanced NSCLC, including platinum-based chemotherapy, anti-PD-1 therapy, and/or other targeted therapies.
- Diagnosed histologically or cytologically with stage IIIB or stage IV non-small
cell lung cancer (NSCLC) or patients with recurrence or progression following
multimodal treatments (radiotherapy, surgical resection, or therapeutic
chemoradiotherapy for locally advanced disease).
- At Least One Measurable Lesion:
- The measurable lesion must not undergo radiotherapy during the cell therapy period.
- Age:
- ≥20 years.
- Weight:
- Between 40 and 100 kg.
- Normal Blood Count (based on test results within 4 weeks before blood collection for
cell preparation):
- White blood cells (WBC): ≥3000/mm³.
- Lymphocytes: ≥1000/mm³.
- Hemoglobin: ≥10 g/dL.
- Platelets: ≥100,000/mm³.
- Normal Liver and Kidney Function (based on test results within 4 weeks before blood
collection for cell preparation):
- Creatinine: ≤1.25× the upper limit of normal (ULN).
- Total bilirubin: ≤1.5× ULN.
- SGOT (AST): ≤3× ULN.
- SGPT (ALT): ≤3× ULN.
- Informed Consent:
- Participants must sign the consent form.
- ECOG Performance Status:
- Score of 0-1.
- For Women of Childbearing Age:
- Must agree to use effective contraception during the trial.
Exclusion Criteria:
- Positive Test Results for the Following Infections:
- HCV (HCV antibody-positive).
- HBV (HBsAg-positive).
- HIV (HIV antibody-positive).
- HTLV (HTLV antibody-positive).
- Syphilis (Treponema pallidum antibody-positive).
- Tuberculosis (TB culture-positive).
- HCV (HCV antibody-positive).
- ECOG Performance Status:
- Score of 2-4.
- Albumin Intolerance:
- Participants who cannot tolerate albumin.
- Short Life Expectancy:
- Life expectancy estimated by the physician to be less than 12 weeks.
- Participation in Other Clinical Trials:
- Within 30 days prior to entering this trial.
- Pregnancy or Breastfeeding:
- Positive pregnancy test or currently breastfeeding.
- Other Medical Conditions:
- Immunodeficiency, severe heart or lung dysfunction, coagulation disorders, unresolved side effects from prior cancer therapy (not recovered to CTCAE grade 1), prior transplant surgery, or deemed unsuitable by the physician.
- Noncompliance:
- Unable to adhere to follow-up or examination procedures.
- Concurrent Cancer:
- Other cancers diagnosed within the past 2 years.
- Specific Complications:
- Brain metastases, leptomeningeal disease, or spinal cord compression.