Clinical Study on the Safety and Efficacy of Autologous Immune Cell Therapy for Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 主要终点
- Phase II Primary Outcome: Objective Response Rate (ORR)
研究概览
简要总结
The autologous immune cell induction technology used in this project involves transforming peripheral blood mononuclear cells (PBMC) into autologous DC cells, NK cells, CIK cells and other immune cells through cytokine induction, and then re-administering them to the patients. This therapy utilizes biotechnology to culture the immune cells of cancer patients in vitro and then re-infuse them back into the body, stimulating and enhancing the body's own immune function, killing and inhibiting cancer cells, eliminating small and residual lesions, or achieving the goal of treating cancer by significantly inhibiting the proliferation of residual cancer cells.
详细描述
This project focuses on the DC autologous immunocyte therapy based on the core technology of screening tumor antigen dominant CTL epitope peptides through independent patent technology. It is a cutting-edge research direction in the field of tumor immunotherapy in recent years. The non-engineered DC cells induced by special induction techniques can effectively overcome the shortcomings of the poor therapeutic effect of engineered gene editing technology on solid tumors, and effectively achieve targeted killing of tumors. The DC-CIK immunocyte therapy adopted in this project utilizes the original discovery of HLA-A molecule-restricted tumor-related antigen CTL epitope peptides to modify DC. On the one hand, through subcutaneous injection in vivo, it induces CD8+ T cells to produce CTL with memory function to play a role in eliminating and monitoring the protein with high expression of the tumor antigen source. On the other hand, it induces CD8+ T cells to produce CTL with memory function in vitro, and directly reinfuses CTL to exert the role of eliminating and monitoring the protein with high expression of the tumor antigen source. In the previous experimental studies, the CTL induced by G22 antigen-loaded DC has shown significant "identification" and targeted "killing" capabilities against various solid tumor cell lines and primary tumor cells isolated from tumor tissues. In animal experiments, it also shows the ability to induce the body to produce a strong immune response against various solid tumors such as breast cancer and non-small cell lung cancer, significantly inhibiting tumor growth, prolonging progression-free survival, and showing no obvious toxic side effects, having a promising application prospect. It has high individualization: customized based on the tumor mutation spectrum of patients, avoiding "off-target" damage to normal tissues. It has high safety: clinical studies have shown that the side effects are mild, mainly including injection site reactions or transient fever 37. Combined treatment potential: it can be used in combination with PD-1 inhibitors, chemotherapy or radiotherapy to enhance efficacy.
At present, self-active immune cell therapy based on tumor antigen-specific CTL epitope peptides has achieved significant progress in both research and clinical application in China. Personalized tumor vaccines, targeted immunoregulatory strategies for the tumor microenvironment, and combination treatment strategies are providing new concepts and methods for tumor therapy. In summary, the "Clinical Research on Safety and Effectiveness of Autologous Immune Cell Therapy for Advanced Solid Tumors" is expected to provide a clinical trial basis for the development of safe and effective clinical immunotherapies for patients with solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study where no masking (blinding) is used. The nature of the interventions makes masking infeasible. Participants, care providers, investigators, and outcomes assessors will all be aware of the treatment group assignments.
The key reasons for the open-label design are:
Distinct Procedures: The autologous immune cell therapy requires a specific process of leukapheresis (blood draw) for cell manufacturing, which is not required for participants in the chemotherapy-only control groups.
Different Administration Routes: The dendritic cells (DC) are administered via subcutaneous injection, while the CIK and NK cells are administered via intravenous infusion. These routes and the appearance of the cell products differ visibly from standard intravenous chemotherapy.
Lack of Placebo: The study protocol does not include the manufacture of a matched placebo for the cellular products to mimic the appearance and administration process.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate in this study, an individual must meet all of the following criteria:
- •The participant must voluntarily participate in the study and provide written informed consent。
- •Age ≥ 18 years, male or female.
- •Histologically and/or cytologically confirmed locally advanced or metastatic solid tumor: lung cancer, liver cancer, colorectal cancer, or breast cancer.
- •ECOG (Eastern Cooperative Oncology Group) performance status score ≤
- •Life expectancy ≥ 3 months.
- •Has not received any other cellular immunotherapy within 3 months prior to enrollment.
- •Has at least one measurable lesion according to RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.
- •Adequate organ function, defined as follows:
- •Hematology:
- •White Blood Cell (WBC) count > 3.5 × 10⁹/L Lymphocyte count > 0.9 × 10⁹/L Monocyte count > 0.16 × 10⁹/L Absolute Neutrophil Count (ANC) > 1.5 × 10⁹/L Platelet (PLT) count > 75 × 10⁹/L Hemoglobin (HB) > 75 g/L Blood Biochemistry： Total bilirubin ≤ 1.5 × ULN (Upper Limit of Normal) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present)
- •Coagulation:
- •Prothrombin Time (PT) and International Normalized Ratio (INR) ≤ 1.5 × ULN
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Prior receipt of any salvage chemotherapy, implanted intraperitoneal chemotherapy, targeted therapy, or biological immunotherapy (except: patients whose disease progressed more than 6 months after completing adjuvant, neoadjuvant, or radiosensitizing chemotherapy, or more than 1 month after intraperitoneal chemoperfusion/wash, are eligible, provided chemotherapy-related toxicities have recovered to Grade 1 or below, excluding alopecia).
- •Major surgical procedure within 4 weeks prior to enrollment, with incomplete recovery from side effects.
- •History of any active malignancy within 5 years, except for the specific cancer under investigation in this trial and cured localized tumors such as carcinoma in situ of the cervix, basal cell carcinoma of the skin, and prostate carcinoma in situ.
- •Presence of more than a small amount of pericardial effusion, or uncontrolled pleural or peritoneal effusion, defined as: detectable by physical examination at screening, or requiring therapeutic paracentesis during the screening period.
- •Inability to tolerate peripheral blood collection due to various reasons (e.g., severe coronary heart disease, inability to establish peripheral venous access).
- •Severe cardiovascular disease, including uncontrolled hypertension, unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > NYHA (New York Heart Association) Class III, or severe arrhythmia.
- •Active infection, unexplained fever ≥ 38.5°C within 7 days prior to medication, or baseline white blood cell count > 15×10⁹/L; OR any severe acute or chronic infection requiring systemic antibacterial, antifungal, or antiviral therapy at screening (except for active hepatitis).
- •Any active autoimmune disease or history of autoimmune diseases (e.g., but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; Patients with vitiligo; Patients with childhood asthma that has completely resolved in adulthood without any intervention are eligible; Asthma requiring bronchodilator medical intervention is excluded). Patients are eligible if: they have a history of autoimmune-related hypothyroidism and are on stable thyroid hormone replacement therapy; or have type I diabetes controlled by insulin therapy.
- •History of drug allergy.
- •Pregnant or lactating women; OR women of childbearing potential or men with pregnant partners who are unwilling to use adequate contraception during the planned trial period (from the screening visit until 120 days after the last study treatment).
- •History of organ transplantation.
- •Any other condition that, in the investigator's judgment, would make the participant unsuitable for the study.
研究组 & 干预措施
Experimental Group
This arm includes all participants who receive the investigational autologous immune cell therapy (either DC-CIK or NK cells), either alone or in combination with chemotherapy. It consolidates the following original arms:
Phase I - DC-CIK Therapy Arm Intervention Name: Autologous DC-CIK Cells
Phase I - NK Therapy Arm Intervention Name: Autologous NK Cells
Phase II - DC-CIK + Chemotherapy Arm Intervention Name: Autologous DC-CIK Cells+Standard Chemotherapy
Phase II - NK + Chemotherapy Arm Intervention Name:Autologous NK Cells+Standard Chemotherapy
干预措施: Autologous immune Cells (Biological)
Experimental Group
This arm includes all participants who receive the investigational autologous immune cell therapy (either DC-CIK or NK cells), either alone or in combination with chemotherapy. It consolidates the following original arms:
Phase I - DC-CIK Therapy Arm Intervention Name: Autologous DC-CIK Cells
Phase I - NK Therapy Arm Intervention Name: Autologous NK Cells
Phase II - DC-CIK + Chemotherapy Arm Intervention Name: Autologous DC-CIK Cells+Standard Chemotherapy
Phase II - NK + Chemotherapy Arm Intervention Name:Autologous NK Cells+Standard Chemotherapy
干预措施: Standard chemotherapy (Drug)
Control Group
This arm includes all participants who receive standard chemotherapy alone, without any investigational cell therapy. It consolidates the following original arms:
Phase II - Chemotherapy Control Arm (HLA-A Positive)
Phase II - Chemotherapy Control Arm (HLA-A Negative)
干预措施: Standard chemotherapy (Drug)
结局指标
主要结局
Phase II Primary Outcome: Objective Response Rate (ORR)
时间窗: From randomization until disease progression, assessed up to approximately 24 months
The proportion of participants who achieve a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Phase I Primary Outcome: Incidence of Adverse Events (AEs)
时间窗: From cell infusion up to 3 months after the last infusion
The safety and tolerability of the autologous immune cell therapies (DC-CIK and NK) will be assessed by the incidence, type, and severity of adverse events. All AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
次要结局
- Duration of Response (DoR)(From the first documented response (CR or PR) until disease progression or death, assessed up to approximately 24 months)
- Time to Recurrence (TTR)(From the start of treatment until disease recurrence, assessed up to approximately 24 months)
- Progression-Free Survival (PFS)(From the start of treatment (Phase I) or randomization (Phase II) until disease progression or death from any cause, assessed up to approximately 24 months)
- Overall Survival (OS)(From the start of treatment (Phase I) or randomization (Phase II) until death from any cause, assessed up to approximately 36 months)
- Disease Control Rate (DCR)(From the start of treatment until the end of 4 treatment cycles, assessed up to 4 months)