CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Age 18-75 years, male or female;
2. Imaging findings showing multiple pulmonary nodules persisting after one year of follow-up, clinically diagnosed as multiple lung cancers by two associate senior or higher-level radiologists, two associate senior or higher-level thoracic surgeons, and one associate senior or higher-level oncologist, with patients refusing continued observation;
3. Patients with a history of surgical resection and pathological diagnosis of NSCLC, who subsequently show disease progression on imaging (progression of primary lesion or new nodules) during follow-up or after targeted therapy, diagnosed as lung cancer by a multidisciplinary expert team, and who refuse surgery or other treatments;
4. Ability to obtain a tumor sample of approximately 1-1.5 cm³ via surgery, biopsy, or bronchoscopy for preparation of autologous tumor-infiltrating lymphocytes;
5. ECOG performance status score of 0-2;
6. HGB ≥70 g/L, transfusion-eligible;
7. No severe hepatic, renal, cardiac, or pulmonary dysfunction, meeting the following criteria:

   Creatinine ≤ 1.5 × ULN; Oxygen saturation \> 90%; Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN;
8. Estimated survival \> 5 years with complete clinical documentation.

Exclusion Criteria:

1. Patients with pathological diagnosis of small cell lung cancer components;
2. Suspicious lesions appearing and follow-up duration less than six months, or remission after anti-inflammatory treatment;
3. Previous history of allogeneic organ transplantation or cytoreductive therapy including lymph node clearance;
4. Patients currently undergoing steroid therapy;
5. Concurrent severe or persistent infections unresponsive to effective control;
6. Concurrent severe autoimmune disease or congenital immunodeficiency;
7. History of severe allergic reactions to biological products (including antibiotics);
8. Active hepatitis (quantitative hepatitis B virus DNA \[HBV-DNA\] above the lower limit of detection for the assay method, or positive hepatitis C antibodies \[HCV-Ab\] with HCV-RNA above the assay method's lower limit of detection);
9. HIV infection or syphilis infection;
10. Female patients who are pregnant, breastfeeding, or planning pregnancy within 12 months;
11. Conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.

主要终点：According to the incidence of treatment-related adverse events（AEs）to evaluate the safety of Tumor-Infiltrating Lymphocytes (TILs) therapy for multiple primary early-stage Non-Small Cell Lung Cancer （NSCLC） · Incidence of treatment-related adverse events（AEs）Description: Number and severity of adverse events graded according to CTCAE v5.0. · up to three years
次要终点：According to the subgroup analysis of TILs in patients with multiple primary early-stage NSCLC to analyze the correlation between TILs and disease prognosis

• A single-arm TILs treatment · EXPERIMENTAL · Experimental: Surgically collect fresh tumor tissue or malignant pleural effusion to isolate immune cells, and prepare TILs Infusion. Trial product: TILs Injection. Administration route: Intravenous Infusion

This is a single-arm study aimed at evaluating the safety of TILs therapy for multiple primary early-stage NSCLC