Her2 and TGFBeta Cytotoxic T Cells in Treatment of Her2 Positive Malignancy

The patient will give blood to grow T cells on either one to two separate occasions. Then,
the EBV-specific T cells will be made. These cells will be grown and frozen. To get the HER2
antibody (and the CD28) and the DNR to attach to the surface of the EBV-T cells, the antibody
gene and the DNR gene will be inserted into the EBV-T cell. This is done with two viruses
called retroviruses that have been made for this study. One will carry the antibody gene into
the T cell and the other the DNR gene.

When the patient is enrolled on the study, they will be assigned to a dose of HER2-DNR EBV-T
cells. The subject will be given one dose of cells into the vein through an IV line. The
injection will take between 1 and 10 minutes. The patient will be followed in the clinic
after the injection for 1 to 4 hours. The treatment will be given by the Center for Cell and
Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

INCLUSION CRITERIA:

The patient must meet the following eligibility inclusion criteria at the time of
PROCUREMENT:

1. Diagnosis of advanced stage* or metastatic HER2-positive cancer (Immunohistochemistry
or reverse transcription-polymerase chain reaction (RT-PCR) is used to determine HER2
positivity)

Definitions of Malignancies and Advanced Stages:

Breast ≥Stage IIIb Colon cancer ≥Stage IIIb Esophageal cancer ≥Stage IIIb Gastric
carcinoma ≥Stage IIIb Head and Neck cancer Stage IV Lung cancer ≥Stage IIIb Pancreatic
cancer Stage IV Prostate cancer Stage IV

*it is expected that the majority of patients who will be accrued on the protocol will
have one of the HER2-positive malignancies listed in the table. If the patient's
malignancy is not listed we will use ≥ Stage IIIb as the definition of advanced stage
disease. If Stage IIIb is not part of the staging system for the individual tumor,
Stage IV will be used.

For World Health Organization grade III and IV brain tumors):patients will be
eligible, who have recurrent or progressive disease after front line therapy.

2. Karnofsky/Lansky score of 50 or more

3. EBV seropositive

4. Greater than or equal to 3 years old

5. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.

The patient must meet the following eligibility criteria to be included for TREATMENT:

1. Diagnosis of advanced stage* or metastatic HER2-positive cancer with disease
progressed after receiving at least one prior systemic therapy. (Immunohistochemistry
or RT-PCR is used to determine HER2 positivity) *for definition refer to Table above.

2. Greater than or equal to 3 years old.

3. EBV-seropositive

4. Recovered from the acute toxic effects of all prior chemotherapy at least a week
before entering this study.

5. Normal echocardiogram (Left ventricular ejection fraction (LVEF) has to be with in
normal, institutional limits)

5. Life expectancy 6 weeks or more

7. Karnofsky/Lansky score of 50 or more

8. Bilirubin 3x or less, Aspartate aminotransferase (AST) 5x or less, Serum creatinine 2x
or less upper limit of normal, Hgb 9.0 g/dl or more, white blood cells greater than
2,000/ul, absolute neutrophil count greater than 1,000/ul, Platelets greater than
100,000/ul

9. Pulse oximetry 90% or more on room air

10. Sexually active patients must be willing to utilize one of the more effective birth
control methods for 6 months after the CTL infusion. Male partner should use a condom.
Acceptable forms of birth control include: * oral contraceptives ("the pill"), *
intrauterine devices (IUDs), * contraceptive implants under the skin, or contraceptive
injections, * condoms with foam.

11. Available autologous transduced EBV-specific cytotoxic T lymphocytes with 15% or more
expression of HER2 CAR determined by flow-cytometry and killing of Her2-positive targets
20% or more in cytotoxicity assay.

12. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent

Note: Patients must also not receive antineoplastic drugs while on this study since they
would kill the infused T cells.

EXCLUSION CRITERIA:

At time of Procurement:

1. Known HIV positivity

At time of Treatment:

1. Severe intercurrent infection

2. Known HIV positivity

3. Pregnant or lactating

4. History of hypersensitivity reactions to murine protein-containing products