Engineered Immune Effectors Against Cervical Cancer

Cervical cancer (CC) is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of the cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, CC is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of CC consists of surgical intervention, radiation, chemotherapy and immunotherapy.

Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of CC-specific engineered immune effectors including cytotoxic T lymphocytes in patients.

Inclusion criteria

• Written, informed consent obtained prior to any study-specific procedures.
• Age older than 10 years.
• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
• Expected survival ≥ 12 weeks.
• Not pregnant, and on appropriate birth control if of childbearing potential.
• Evidence of high-risk HPV infection.
• Stage III-IV or recurrent cervical cancer.
• Initial hematopoietic reconstitution with

• neutrophils (ANC) ≥ 1,000/mm^3;
• platelet (PLT) ≥ 100,000/mm^3.
• Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

• serum creatinine ≤ 2×ULN;
• serum bilirubin ≤ 2×ULN;
• AST/ALT ≤ 2×ULN;
• ALKP ≤ 5×ULN;
• serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.
• Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test negative.

Exclusion criteria

• Patients with

• cervical benign lesions: cervical columnar epithelium ectopic, cervical polyps, cervical endometriosis and cervical tuberculous ulcers;
• cervical benign tumors: cervical submucous myoma, cervical cancer, cervical papilloma.
• Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
• Previous exposure to mouse SCC antibody.
• Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
• Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).
• Pregnant or lactating females.
• Inadequate bone marrow function with

• absolute neutrophil count < 1,000/mm^3;
• platelet count < 100,000/mm^3;
• Hb < 9 g/dL.
• Inadequate liver and renal function with

• serum (total) bilirubin > 1.5 x ULN;
• AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases);
• alkaline phosphatase > 2.5 x ULN;
• serum creatinine >2.0 mg/dl (> 177 μmol/L);
• urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
• Serious active infection requiring i.v. antibiotics at during screening.
• Subject actively infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.