Treatment of Chemotherapy Refractory Human Epidermalgrowth Factor Receptor-2( HER-2) Positive Advanced Solid Tumors
Treatment of Chemotherapy Refractory Human Epidermalgrowth Factor Receptor-2( HER-2) Positive Advanced Solid Tumors
RATINALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory
 into patient autologous T cells may make the body build immune response to kill cancer cells.

 PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in
 treating patients with HER-2 positive advanced solid tumors,such as breast cancer, gastric
 cancer, hepatic carcinoma, endometrial cancer and ovary cancer.
PRIMARY OBJECTIVES:

 I.Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
 with anti-HER-2 vector(referred to as CART-HER-2 cells).

 II.Determine duration of in vivo survival of CART-HER-2 cells. RT-PCR(reverse transcription
 polymerase chain reaction)analysis of whole blood will be used to detect and quantify
 survival of CART-HER-2 TCR zeta:CD137 and TCR(T-cell receptor) zeta cells over time.

 SECONDARY OBJECTIVES:

 I.For patients with detectable diseases, measure anti-tumor response due to CART-HER-2 cell
 infusions.

 II.Estimate relative trafficking of CART-HER-2 cells in tumor bed.

 III.Determine if cellular or humoral host immunity develops against the murine anti-HER-2,
 and assess correlation with loss of detectable CART-HER-2(loss of engraftment).

 IV.Determine the relative subsets of CART-HER-2 T cells (Tcm,Tem,and Treg).

 OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive
 anti-HER-2-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced
 autologous T cells on days 0,1, and 2 in the absence of unacceptable toxicity.

 After completion of study treatment, patients are followed intensively for 6 months, every 3
 months for 2 years, and annually thereafter for 13 years.

 Estimate relative trafficking of CART-HER-2 cells in peripheral blood.
Inclusion Criteria:

 -  Chemotherapy refractory HER-2-positive breast cancer, gastric cancer, non-small cell
 lung cancer, and chemotherapy resistant or relapsed ovary cancer.

 -  Relapsed patients after anti-HER-2 using antibody or kinase inhibitor therapy.

 -  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(2).

 -  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:

 -  Patients with life expectancy less than 12 months will be excluded.

 -  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.

 -  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.

 -  Patients with history of T cell tumors will be excluded.

 -  Patients who are participating or participated any other clinical trials in latest 30
 days will be excluded.