HPV16 E6 TCR T Cells for Cervical Carcinoma

Prior treatment

• Received any other investigational treatment within 4 weeks before the first administration or enrolled in another clinical trial the same time (exception: the other treatment is observational and non-investigational or the patient is under follow-up period)
• Patients with active autoimmune disease or require systemic steroid treatment. (except patients with cutaneous condition but without systemic treatment, or subjects with asthma in childhood but without intervention after grown-up, or subjects with hypothyroidism mediated by autoimmune dysfunction and receiving thyroxine as replaced treatment)
• Treponema pallidum antibody positive.
• Received major surgery or under severe injury within 4 weeks before enrollment.
• Received cell therapy before enrollment，such as TCR-T，CAR-T and TIL .
• Received treatment related chemo-therapy within 14 days of TC-E202 infusion (except lymphodepletion) .

Other illness

• Severe allergic to related ingredients in the clinical trial.
• Primary central nerve system (CNS) cancer, or subjects with CNS metastasis after localized treatment (except patients without CNS metastasis, clinically stable and neither steroid treatment nor treatment for CNS metastasis).
• Immunodeficiency including HIV positive, harvested or natural immunodeficiency.
• Patients with hereditary or acquired hemorrhagic disease
• Patients with cardiovascular disease or symptoms:
  • congestive heart failure (NYHA > 2); history of unstable angina pectoris; miocardial infarction within 48 weeks; clinically significant malignant arrhythmia (except atrial fibrillation and paroxysmal supraventricular tachycardia); Clinically significant prolonged QTcF (Male QTcF > 450 msec, Female QTcF > 470 msec); Uncontrolled hypertension.
• Patients under active infection (except subjects with fever caused by tumor)
• Patients with active tuberculosis, or history of active tuberculosis within 1 year before enrollment, or history of active tuberculosis over a year before enrollment but without standard treatment.
• Patient with Active Hepatitis B or Active Hepatitis C.
• History of drug abuse, alcohol or drug addiction.
• Allergic to IL-2.

Other

• Under pregnancy or lactation, or positive based on blood pregnancy test.
• Patients with ≥ grade 3 thromboembolic events within 2 years or under thrombolysis treatment.
• Patient not suitable for the clinical trial according to investigators.

• Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial.
• Age ≥ 18 years and ≤ 70 years.
• Expected survival time > 3 months.
• ECOG score 0-1.
• Recurrent or metastatic cervical carcinoma based on TNM \& FIGO staged histopathological investigation.
• Received at least second-line standard treatment and diagnosed as PD through image assessment. (previously received radio-therapy, chemo-therapy, targeted-therapy or immune-therapy, wash-out period > 14 or 5 half life)
• Be able provide fresh or preserved tissue specimen. (fresh specimen first, paraffine specimen or at least 12 tumor section, tumor tissue >20%)
• At least 1 measurable lesion (according to RECIST1.1 standard）.
• HPV16 positive.
• HLA-A2 positive.
• Hematology should at least meet the following criteria:
  • Absolute neutrophil count (ANC) ≥ 1.5× 109/L (±20%)； Platelet (PLT） ≥ 75× 109/L (±20%）； Hemoglobin (HGB) ≥ 90 g/L (±20%).
• Blood biochemistry should at least meet the following criteria:
  • Serum creatinine (Cr) ≤ 1.5 times of upper limit of normal (ULN) or creatine clearance ≥ 60 ml/min; Serum Alanine aminotransferase (ALT) or/and Aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal; Total bilirubin (TBIL) ≤ 15 times of upper limit of normal.
• Blood coagulation function is normal: Prothrombin time (PT) ≤ 1.5 ULN, International Normalized Ratio (INR) ≤ 1.5 ULN, or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 ULN.
• Women of childbearing potential should be ascetic or take contraception since the signing of ICF to 24 weeks or later after the last administration of drug.
• Recovered from toxic effect of previous treatment (CTCAE ≤ 1), or related AE(s) is not defined as safety issue.
• Catheter insertion is feasible and No White Blood Cells collection contraindications.