Overview
The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.
Description
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.
Eligibility
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.
