| Eligibility |
Inclusion Criteria:
1. They voluntarily signed the informed consent form (ICF) and completed the study
procedure and follow-up examination and treatment.
2. Age from 18 to 75 years old, regardless of gender;
3. The ECOG performance status score was 0-1.
4. Advanced solid tumors positive for PAN-CK, confirmed histopathologically or
cytologically: Advanced solid tumors that have failed previous standard therapy
(disease progression or intolerance), currently have no standard treatment options, or
are unable to receive current standard treatment for other reasons Included, but not
limited to, driver gene negative non-small cell lung cancer (NSCLC) (except
neuroendocrine tumors or mixed types containing >10% of neuroendocrine tumors),
primary or metastatic breast cancer (TNBC), and histopathologically or cytologically
confirmed patients with at least one prior platinum-based chemotherapy regimen and no
more than three prior systemic treatment failures (disease progression or intolerance)
Toxicity) of recurrent/metastatic cervical cancer (cervical squamous, adenosquamous,
and adenocarcinoma subjects), ovarian cancer, liver cancer, head and neck cancer, and
colorectal cancer (CRC);
5. Subjects had at least one eligible tumor lesion/tissue for preparation of ReT01 ACT
injection. Fresh cancerous tissue (proximal metastatic lymph node or tumor margin
tissue) with a total tumor volume of at least 0.125 cm3 was obtained by conventional
surgical or interventional methods. The number of re-TILs in tumor tissue that met the
needs of reinfusion and detection was sufficient.
6. The predicted survival time was =3 months.
7. After tumor lesion/tissue sampling, the subject still had at least one measurable
tumor lesion according to Response Evaluation criteria in Solid Tumors, version 1.1
(RECIST 1.1) criteria.
8. Patients with good organ function (no platelet or cell stimulating factor transfusion
within 14 days before enrollment) and laboratory results meeting the following
criteria: 1) absolute neutrophil count (ANC) =1.0×109/L; 2) platelet count (PLT)
=80×109/L; 3) hemoglobin (Hb) =80 g/L; 4) Serum bilirubin (TBIL) =1.5× upper limit of
normal (ULN), if the subject has Gilbert's syndrome or liver metastasis TBIL=3×ULN; 5)
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5×ULN; If liver
metastasis existed, ALT and AST=5×ULN; 6) international normalized ratio (INR)
=1.5×ULN, activated partial thromboplastin time (APTT) =1.5×ULN (except those on
anticoagulant therapy); 7) creatinine clearance =60 mL/min (calculated by
Cockcroft-Gault formula);
9. Toxic effects from previous therapy had resolved to grade 1 or less before enrollment
(with the exception of grade 2 or less neurotoxicity from alopecia and
chemotherapeutic agents).
10. Women of childbearing age who had a negative blood pregnancy test within 7 days before
enrollment; Any male and female patient of childbearing potential must agree to use
effective contraception for at least 6 months from enrollment until infusion of the
ReT01 ACT injection. According to the investigator's judgment, a patient was
considered to be fertile if the patient was biologically capable of having children
and had a normal sexual life. Infertile women were required to meet at least one of
the following criteria: 1) prior hysterectomy or bilateral oophorectomy, 2) medically
confirmed ovarian failure, 3) medically confirmed, physiologic cessation of
menstruation for at least 12 consecutive months (excluding use of chemoradiotherapy or
estrogen/progestin-based drugs or other pathological factors);
11. The trial protocol was approved and adhered to, as judged by the investigators.
Exclusion Criteria:
1. There were only bone metastases.
2. Central nervous system metastases were present.
3. He had received other previous adoptive cell therapies.
4. Patients received any systemic anti-tumor therapy (including chemotherapy,
radiotherapy, molecular targeted therapy, etc.) within 3 weeks before conditioning.
5. Chinese/herbal medicine with anti-tumor indications was received within 1 week before
pretreatment.
6. Treatment with prednisone at a dose of 10 mg or more per day or its equivalent
systemic corticosteroids (except for inhaled, topical, or physiological replacement
therapy) or other immunosuppressive medications within 2 weeks before conditioning.
7. Any major surgery within 4 weeks before screening that was considered by the
investigator to be unsuitable for enrollment or any other planned major surgery during
the study (excluding the planned surgery for the preparation of Re-TIL cells as
specified in the protocol) (The definition of major surgery was based on the grade 3
and 4 procedures specified in the Administrative Measures for the Clinical Application
of Medical Technology implemented on May 1, 2009). ;
8. Patients with other malignant tumors within 5 years before screening or at the same
time (patients with locally treated malignant tumors that did not require treatment
for more than 1 year and had no significant risk of recurrence according to the
investigator's judgment were excluded, including but not limited to non-melanoma skin
cancer, bladder cancer, etc.);
9. A history of active or suspected autoimmune or inflammatory disease;
10. Previous history of organ transplantation or hematopoietic stem cell transplantation;
11. Presence of any of the following infections: 1) active hepatitis B (hepatitis B
surface antigen [HbsAg] positive and hepatitis B virus DNA [HBV-DNA] > 1000 copies
/ml); 2) active hepatitis C (positive for hepatitis C virus (HCV) antibody and HCV RNA
(HCV-RNA) test > the lower limit of study detection); 3) active systemic infections
requiring antibiotics (e.g., sepsis, bacteremia, fungemia, etc.); 4) congenital or
acquired immunodeficiency (including but not limited to severe combined
immunodeficiency disease, human immunodeficiency virus (HIV) infection, etc.);
12. Vaccination with a live or attenuated vaccine within 4 weeks before conditioning;
13. Patients with severe cardio-cerebrovascular disease including but not limited to: 1)
hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100
mmHg) that is poorly controlled with medical therapy; 2) previous history of
hypertensive crisis or hypertensive encephalopathy; 3) cardiovascular and
cerebrovascular events, transient ischemic attack, myocardial infarction, unstable
angina, and significant vascular disease (including but not limited to aortic aneurysm
or proximal arterial thrombosis requiring surgical repair) within 6 months before
enrollment; 4) New York Heart Association (NYHA) class =II heart failure with left
ventricular ejection fraction (LVEF) <50%; Severe arrhythmias uncontrolled by
medication (including QTc interval =450 ms in men or =470 ms in women, calculated
according to Fridericia's formula), ongoing or planned use of medications that may
prolong the QT interval, or congenital long QT syndrome;
14. Severe respiratory disease (previous or combined history of severe interstitial lung
disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency,
or symptomatic bronchospasm); Forced expiratory volume in 1 second (FEV1) <2 L, carbon
monoxide diffusion capacity (DLCO) (calibrated) <40%;
15. A clear previous history of a neurological or psychiatric disorder, including epilepsy
or dementia;
16. A history of severe allergic reactions to drugs used during the study (including but
not limited to cyclophosphamide, fludarabine, IL-2, components of ReT01 ACT injection,
gentamicin, etc.);
17. Other conditions considered by the investigator to be inappropriate for participation
in the trial (e.g., grade 3 or higher adverse effects from previous immunotherapy).
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