| Eligibility |
Inclusion Criteria:
- Participants who meet all of the following criteria are eligible for admission to the
study:
1. 18= age =75 years old, male or female;
2. Patients with incurable advanced gastric cancer, esophageal cancer, cervical
cancer, triple-negative breast cancer, non-small cell lung cancer, and other
malignancies who have failed standard treatment (standard treatment failure is
defined as those treated according to the 2022 CSCO Guidelines and whose tumor
efficacy is assessed as disease progression (PD) or tumor recurrence or inability
to tolerate existing treatment options);
3. There are tumor tissues or cancerous exudative thoracoabdominal fluid that can be
used to isolate TRTs: the total volume of the solid tissue taken must be
> 0.5cm3 or the weight must be >0.5g, the cancerous
exudative thoracoabdominal fluid taken should contain at least 5×10^8 total
cells, and the lesions taken have not been treated with oncolytic virus.
4. There is at least one measurable lesion (according to RECIST1.1 criteria) even
after TRTs sampling/puncture biopsy;
5. ECOG score 0-1;
6. The expected survival period is greater than 3 months;
7. Sufficient hematology and end-organ function, as defined by the following
laboratory test results, should be completed within 14 days prior to TRTs tumor
tissue collection:
1. Blood routine: white blood cell count =2.5×10^9/L; Absolute neutrophil count
(ANC) =1.5×10^9/L; Absolute lymphocyte count (ALC) =1.0×10^9/L; Platelet
(PLT) =80×10^9/L; Hemoglobin (HGB) =90g/L;
2. Coagulation function: International standardized ratio of prothrombin time
(INR) =1.5×ULN; Partial prothrombin time (APTT) =1.5×ULN, unless
anticoagulant therapy has been received within the previous 7 days;
3. Renal function: serum creatinine =1.5mg/dL (or 132.6µmol/L) or creatinine
clearance =60mL/ min;
4. Liver function: aspartate aminotransferase (AST/SGOT) =3×ULN; Alanine
transaminase (ALT/SGPT) =3×ULN; Total bilirubin (TBIL) =1.5×ULN; Note: In
patients with liver metastasis or primary liver tumor, aspartate and alanine
aminotransferase should be =5×ULN; For patients with a history of Gilbert
syndrome or suspected Gilbert syndrome, total bilirubin (TBIL) should be
=3×ULN;
5. Urine routine: urinary protein <2+, or 24-hour urinary protein
quantity <1g;
6. Left ventricular ejection fraction (LVEF) =50% by echocardiography;
7. Pulmonary function tests with FEV1>60% or
FEV1/FVC>0.7;
8. Blood oxygen saturation = 93%.
8. Women of childbearing age who have a negative urine pregnancy test during
screening and baseline and agree to use highly effective contraception for at
least 1 year after the infusion; Male subjects whose partners are fertile must
agree to use effective contraceptive methods and refrain from sperm donation for
at least 1 year after the infusion;
9. No absolute or relative contraindications to surgery or puncture;
10. Any treatment for malignant tumors, including radiotherapy, chemotherapy,
endocrine therapy, targeted therapy, tumor embolization, or Chinese
medicine/herbal therapy with anti-tumor indications, must be discontinued 7 days
before TRT sampling;
11. Sign a written informed consent (ICF) voluntarily, and have good compliance with
the protocol requirements for visits or planned visits and other relevant
research procedures.
Exclusion Criteria:
- Subjects who meet any of the following criteria will not be eligible to participate in
this clinical trial:
1. Prior allergy to cyclophosphamide, fludarabine and interleukin-2
contraindications or to any component of the infusion product formulation or to
other drugs to be used during the study (antibiotics, human serum albumin,
dextran 40, etc.);
2. Any NCI CTCAE5.0 immune-related adverse reaction (irAE) grade >3 that
has been permanently discontinued during any previous immunotherapy;
3. Patients with prior primary immunodeficiency and active autoimmune disease;
4. Previous history of organ allotransplantation, allogeneic stem cell
transplantation and kidney replacement therapy;
5. Patients with current or past irreversible interstitial lung disease (except
those caused by radiotherapy);
6. Combined with 2 or more malignant tumors; (Except for the following cases:
malignant tumors that have been cured, such as non-melanoma skin cancer and in
situ cervical cancer, bladder cancer, breast cancer, thyroid cancer, etc. that
have survived more than 5 years without disease.)
7. Uncontrolled co-morbidity includes, but is not limited to, uncontrolled
hypertension (systolic blood pressure =160mmHg and/or diastolic blood pressure
=100mmHg) even after standard treatment, or any unstable cardiovascular and
cerebrovascular disease, including transient ischemic attack, cerebrovascular
accident, myocardial infarction, and unstable angina pectoral, that has occurred
in the 6 months prior to treatment induction; Congestive heart failure rated III
or IV by the New York Heart Association (NYHA); Ejection fraction <
50%; Severe heart rhythm or conduction abnormalities, such as ventricular
arrhythmias requiring clinical intervention, degree II-III atrioventricular
block, etc. Electrocardiogram results show clinically significant abnormalities,
or QTcF=450ms (if the first examination is abnormal, the interval of at least 5
minutes, retest twice, using the comprehensive result/average value to judge
eligibility);
8. Patients with esophageal or gastric varices that require immediate intervention
(such as ligation or sclerotherapy) or are considered by the investigator or
gastroenterologist or hepatologist to be at high risk of bleeding, have evidence
of portal hypertension (including splenomegalysis on imaging), or have a history
of varicose bleeding must undergo endoscopic evaluation within 3 months prior to
enrollment;
9. Uncontrolled metabolic disorders, such as in patients with diabetes, or other
non-malignant organ or systemic disease or cancer secondary reactions that can
lead to higher medical risk and/or uncertainty in the evaluation of survival;
10. Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade C or more severe
cirrhosis, liver failure;
11. Clinically uncontrollable third space effusion, such as pleural fluid and ascites
that could not be controlled by drainage or other methods before enrollment;
12. Combined with other serious organic disease or mental illness;
13. Patients with central nervous system metastasis;
14. Uncontrolled systemic active infection;
15. Receive vaccination within 2 months before signing the informed consent, or plan
to receive vaccination during the study;
16. Currently or within 30 days before signing the informed consent to participate in
clinical trials of other drugs or biotherapeutics, except cell therapy that has
been fully metabolized;
17. have used within 4 weeks prior to the treatment, or have concomitant disease or
active autoimmune disease that the investigator determined required the use of
glucocorticoids or other immunosuppressive drugs during the trial period,
excluding local percutaneous absorption of glucocorticoids (i.e., no more than 5
mg/ day of prednisone or equivalent doses of other glucocorticoids);
18. Surgical treatment, interventional therapy, radiotherapy, chemotherapy and
immunotherapy for the studied disease were performed within 2 weeks before the
treatment;
19. HIV positive, serological test positive for syphilis, or clinically active
hepatitis B or C, including carriers of the virus (for hepatitis B, HBsAg
positive persons should be excluded; For hepatitis C, HCVAB-positive patients
need to be excluded);
20. Women who are breastfeeding during pregnancy or lactation;
21. Poor compliance due to physiological, family, social, geographical and other
factors, unable to cooperate with the study protocol and follow-up plan;
22. Other conditions deemed unsuitable for participation in this experiment by the
researcher.
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