自体细胞治疗用于肺癌、肝癌：I/II 期临床试验（Liaoning Medical）

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all of the following criteria:

1. The participant must voluntarily participate in the study and provide written informed consent。
2. Age ≥ 18 years, male or female.
3. Histologically and/or cytologically confirmed locally advanced or metastatic solid tumor: lung cancer, liver cancer, colorectal cancer, or breast cancer.
4. ECOG (Eastern Cooperative Oncology Group) performance status score ≤ 2.
5. Life expectancy ≥ 3 months.
6. Has not received any other cellular immunotherapy within 3 months prior to enrollment.
7. Has at least one measurable lesion according to RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1.
8. 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

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. 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).
2. Major surgical procedure within 4 weeks prior to enrollment, with incomplete recovery from side effects.
3. 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.
4. 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.
5. Inability to tolerate peripheral blood collection due to various reasons (e.g., severe coronary heart disease, inability to establish peripheral venous access).
6. 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.
7. 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).
8. 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.
9. History of drug allergy.
10. 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).
11. History of organ transplantation.
12. Any other condition that, in the investigator's judgment, would make the participant unsuitable for the study.

主要终点：Phase II Primary Outcome: Objective Response Rate (ORR) · 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. · From randomization until disease progression, assessed up to approximately 24 months；Phase I Primary Outcome: Incidence of Adverse Events (AEs) · 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. · From cell infusion up to 3 months after the last infusion
次要终点：Progression-Free Survival (PFS)；Overall Survival (OS)；Disease Control Rate (DCR)；Duration of Response (DoR)；Time to Recurrence (TTR)

• Experimental Group · EXPERIMENTAL · 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
• Control Group · ACTIVE_COMPARATOR · 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)

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.