This is a single-center, single-arm, prospective clinical trial to investigate the safety and efficacy of Neo-DCVac combined with ICIs in the treatment of advanced lung cancer resistant to ICIs.

The study screened patients with PD-1 immunochemotherapy in the first-line treatment regimen, and extracted tumor tissues from patients after PD-1 resistance for neoantigen prediction. During neoantigen screening and vaccine preparation, patients received a second-line regimen (docetaxel) as bridging therapy. After completion of bridging therapy and the patient 's vaccine preparation was successful, the patient started receiving the vaccine combined with ICIs. The completion of 5 vaccine injections was followed by an immunization course. Efficacy was assessed 2 weeks after the end of an immunization course, and if effective (tumor response evaluated as SD/PR/CR), the next cycle of immunotherapy was continued, with subsequent treatments administered every 3 weeks until disease progression or severe intolerance occurred or the patient requested withdrawal, whichever came first.

Inclusion Criteria:

• Aged 18-85 years.
• ECOG score was 0-2.
• Histological or cytological diagnosis confirmed non-small cell lung cancer, which was staged IIIB-IV according to AJCC version 8.
• Patients have received first-line chemotherapy combined with ICIs (PD1/PD-L1, ICIs type is not limited) and developed drug resistance.
• Normal function of major organs, that is, meeting the following criteria: a) blood routine examination (hematopoietic growth factors and blood transfusion were not used within 7 days): granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 80 g/L; b) biochemical examination: total bilirubin ≤ 1.5 × ULN (upper limit of normal); serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula); c) coagulation function: INR or PT ≤ 1.5 × ULN (upper limit of normal), if the subject is receiving anticoagulant therapy, as long as PT is in the range proposed by anticoagulant drugs; d) urine routine examination: urine routine examination urine protein ≥ 2 +, 24-hour urine protein quantitative examination should be performed, such as quantitative urine protein ≤ 1 g/24 h.
• Female subjects of childbearing age or male subjects with sexual partners of childbearing age should take effective contraceptive measures throughout the treatment period and 6 months before and after the treatment period.
• Subjects voluntarily participate in the study and sign the informed consent form

Exclusion Criteria:

• The pathological type is mixed type, containing small cell carcinoma or other types of components.
• with the blood-borne infectious disease HIV.
• History of mental disorder, drug abuse and drug abuse.
• Any other malignancy (except completely cured cervical carcinoma in situ or basal cell or squamous cell skin cancer) within 3 years.
• Accompanied by other immune diseases, or long-term use of immunosuppressive agents or hormones.
• Any unstable systemic disease (including active uncontrolled gastrointestinal ulcers, gastric obstruction, bleeding risk or coagulopathy, active infection, for subjects with hepatitis B, anti-hepatitis B 11 virus treatment is required during study treatment, active hepatitis C subjects (HCV antibody positive and HCV- RNA levels above the lower limit of detection, grade IV hypertension, unstable angina pectoris, congestive heart failure, myocarditis, unstable cerebrovascular disease, thrombotic disease, liver, kidney, uncontrolled metabolic disease or unhealed fractures, wounds as judged by the surgeon).
• Presence of active central nervous system (CNS) metastases; subjects with previously treated brain metastases (e.g., surgery, radiotherapy, hormone therapy) are allowed if clinically stable for at least two weeks after treatment from the first dose of study drug and corticosteroids are discontinued 7 days before study drug administration; untreated, asymptomatic subjects with brain metastases (i.e., no neurological symptoms, no need for corticosteroids, no significant edema around the brain metastases) can be enrolled.
• Any anti-tumor therapy including chemotherapy, radiotherapy, and targeted therapy within 3 weeks prior to the first dose of study drug.
• Presence of pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring drainage.
• Previous use of anti-tumor vaccines, live vaccines within 30 days.
• Patients are difficult to communicate or to follow up for a long time. Pregnant or lactating women.
• Current or planned participation in other clinical trials.
• Dr. finds other unsuitable situations