Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells for Gastric/Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria:

1. Age: 18-70 years old (including the threshold);
2. Subject has pathologically confirmed locally advanced or metastaticgastric/gastroesophageal junction adenocarcinoma：Having received at least one standardtreatment, with the disease in stable or progressive state, and the subject refusingfurther treatment or intolerant to existing therapies; Failing second-line treatment;
3. Subject's freshly biopsied tumor tissue (if the patient has not received targetedClaudin18.2 therapy, archived tumor tissue within one year is acceptable) hasimmunohistochemistry confirmed positive expression of Claudin18.2;
4. Subject has predicted life expectancy ≥ 90 days;
5. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
6. Subject is willing to undergo tumor biopsy;
7. Subject has at least one measurable tumor lesion on imaging (per RECIST 1.1 criteria);
8. Female subjects of childbearing age must not be lactating, and sensitive serumpregnancy test during the screening period must be negative for fertile women. Allsubjects must use medically accepted contraceptive measures (such as intrauterinedevices, contraceptives) throughout the treatment period and 1 year after cellinfusion. Male subjects must also avoid sperm donation;
9. Subject has adequate organ function reserves: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Absolute lymphocyte count (ALC) ≥ 0.6×109/L; Platelet count ≥ 75×109/L;Hemoglobin ≥ 9.0 g/dL; Total bilirubin ≤ 2 × upper limit of normal (ULN) ; ALT and AST ≤ 2.5 × ULN (or ≤ 5 × ULN if bone or liver metastases are present); Creatinineclearance (Cockcroft-Gault method) ≥ 60 mL/min; Stable coagulation function:Prothrombin time (PT) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 55% withoutmoderate or severe pericardial effusion; Baseline oxygen saturation in room air ≥ 92%;
10. Subject is able to establish intravenous access, and peripheral blood mononuclearcells can be collected according to the investigator's judgment;
11. Subject is willing to sign the informed consent form;
12. Subject can communicate well with the investigator, is willing and able to comply withthe study plan and will complete the study as per the study requirements.

Exclusion Criteria:

1. Subject has a positive test for Hepatitis B surface antigen (HBsAg) or Hepatitis Cvirus antibody (HCV-Ab) or Treponema pallidum antibody (TP-Ab) or HumanImmunodeficiency Virus antibody (HIV-Ab). Subjects who are positive for both hepatitisB core antibody (HBcAb) and HBV deoxyribonucleic acid (DNA) will be excluded.
2. Subject has other malignant tumors, except for: cured non-melanoma skin cancer, insitu cervical carcinoma, localized prostate cancer, superficial bladder cancer, ductalcarcinoma in situ, and other malignant tumors with disease-free survival exceeding 5years.
3. Subject has symptomatic intracranial metastases.
4. Subject has central or extensive lung or liver metastases.
5. Subject with a maximum target lesion > 4.0 cm (per RECIST 1.1 criteria).
6. The subjects' tumor tissue is positive for HER2 expression.
7. Subject has a history of prior anti-tumor treatment or participation in clinicaltrials: subject has received treatment with CAR-T therapy, or other gene-edited celltherapies; subject has participated in other clinical trials within 28 days beforescreening; Subject has received local radiotherapy or small molecule chemotherapywithin 7 days before leukapheresis, or within at least five half-lives (whichever islonger).; subject has received daily systemic corticosteroid ≥ 15 mg within 7 daysbefore leukapheresis, except inhaled corticosteroids.
8. Subject has received vaccination within 28 days before screening.
9. Subject has conditions requiring the use of systemic corticosteroids or otherimmunosuppressive drugs during the study period, as determined by the investigator.
10. Subject has acute toxic reactions from previous treatments not recovered to Grade 1 orlower (excluding hematological toxicity, alopecia, and events considered tolerable bythe investigator).
11. Subject has life-threatening hypersensitivity reactions or other intolerances tocyclophosphamide, fludarabine, or albumin-bound paclitaxel, or severe hypersensitivityto human serum albumin, DMSO, or other substances.
12. Subject underwent general anesthesia within 28 days before screening, or has notrecovered and clinically stabilized after previous surgical treatment, or is expectedto undergo general anesthesia during the study.
13. Subject has any unstable cardiovascular diseases within 180 days before screening,including but not limited to unstable angina, myocardial infarction, heart failure (New York Heart Association [NYHA] class ≥ III), severe arrhythmias requiringmedication, or underwent cardiovascular intervention, coronary artery stenting, orcoronary artery bypass grafting within 180 days before screening.
14. Subject has a disease or history of central nervous system disorders, such asepilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or anyautoimmune diseases involving the CNS.
15. Subject has uncontrolled or requiring intravenous treatment for fungal, bacterial,viral, or other infections at the time of screening.
16. Subject has uncontrolled or active ulcers or gastrointestinal bleeding at the time ofscreening.
17. Subject has active autoimmune diseases (including but not limited to systemic lupuserythematosus, Sjögren's syndrome, rheumatoid arthritis, psoriasis, multiplesclerosis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., with theexception of hypothyroidism that can be controlled only by hormone replacementtherapy).
18. Subject has a bleeding and thrombotic tendency, including: subject who had significantclinically significant bleeding symptoms or definite bleeding tendencies within 90days before screening, subject who has genetic or acquired bleeding and thrombotictendencies (e.g., hemophilia, coagulation disorders, splenic hyperfunction), subjectwho is undergoing thrombolysis or anticoagulant therapy and subject who had events ofarterial/venous thrombosis within 180 days before screening, such as cerebrovasculardisease (including cerebral hemorrhage, cerebral infarction), deep venous thrombosis,and pulmonary embolism.
19. Subject has a history of substance abuse with psychiatric drugs and unable to abstain,or with a history of psychiatric disorders.
20. Subject has other situations in which the investigator deems unsuitable forparticipation in this clinical study.