Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD133 (cluster of differentiation antigen 133 ) vector (referred to as CART-133 cells).

II. Determine duration of in vivo survival of CART-133 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-133 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-133 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-133 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of CART-133 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells determine tumor cell killing by CART-133 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD133, and assess correlation with loss of detectable CART-133 (loss of engraftment).

VI. Determine the relative subsets of CART-133 T cells (Tcm, Tem, and Treg).

Inclusion criteria

• Chemotherapy refractory or relapsed CD133-positive liver cancer, pancreatic cancer, brain tumor ,breast cancer, ovarian tumors, colorectal cancer and acute leukemia.
• Patients must be 18 years of age or older.
• Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
• Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:

Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).

Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m.

• Seronegative for HIV antibody.
• Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
• Patients must be willing to practice birth control during and for four months following treatment. NOTE: women of child-bearing age must have evidence of negative pregnancy test.
• Patients must be willing to sign an informed consent.

Exclusion criteria

• 1. Patients with life expectancy less than 12 months will be excluded. 2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.

• Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.

• Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.

• Pregnant and/or lactating women will be excluded. 6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.

• Patients with any type of primary immunodeficiencies will be excluded from the study.

• Patients requiring corticosteroids (other than inhaled) will be excluded. 9. Patients with history of T cell tumors will be excluded. 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.

• Patients with relapsed acute leukemia after allogeneic stem cell transplantation