A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-Infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers

Inclusion Criteria

-INCLUSION CRITERIA:

1. Measurable metastatic (stage IV) gastric, gastroesophageal, pancreatic,
hepatocellular carcinoma, cholangiocarcinoma, gallbladder, and colorectal carcinomas
with at least one lesion that is resectable for TIL generation with minimal morbidity
preferentially using minimal invasive laparoscopic or thoracoscopic surgery for
removal of superficial tumor deposit.

2. All patients must be refractory to approved standard systemic therapy.

Specifically :

- Metastatic colorectal patients must have received 5-FU and leucovorin in
combination with either oxaliplatin and/or irinotecan, since level 1 evidence
support increase survival with these regimens, compared to 5-FU and leucovorin
alone.

- Hepatocellular carcinoma patients must have received sorafenib
(Nexavar(Registered Trademark)), since level 1 data support a survival benefit
with this agent.

3. Clinical performance status of ECOG 0 or 1.

4. Life expectancy of greater than three months.

5. Greater than or equal to 18 years of age.

6. Willing to practice birth control during treatment and for four months after
receiving the preparative regimen.

7. Willing to sign a durable power of attorney.

8. Able to understand and sign the Informed Consent Document.

9. Hematology:

- Absolute neutrophil count greater than 1000/mm(3) without support of filgrastim.

- Normal WBC (> 3000/mm(3)).

- Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this
cut-off.

- Platelet count greater than 100,000/mm(3).

- Normal prothrombin time (less than or equal to 15.2 seconds).

10. Serology:

- Seronegative for HIV antibody. (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive can have decreased immune competence and thus may be less
responsive to the experimental treatment and more susceptible to its
toxicities.)

- Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
If hepatitis C antibody test is positive, then patient must be tested for the
presence of antigen by RT-PCR and be HCV RNA negative.

11. Chemistry:

- Serum ALT/AST less than five times the upper limit of normal.

- Serum creatinine less than or equal to 1.6 mg/dl.

- Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert?s
Syndrome, who must have a total bilirubin less than or equal to 3 mg/dl.

12. More than four weeks must have elapsed since any prior systemic therapy at the time
the patient receives the preparative regimen, and patients? toxicities must have
recovered to a grade 1 or less. Patients may have undergone minor surgical procedures
with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

13. Six weeks must have elapsed since any prior anti-vascular endothelial growth factor
(VEGF) or anti-tyrosine kinase receptors (TKR) therapy to allow antibody levels to
decline.

EXCLUSION CRITERIA:

1. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

2. Systemic steroid therapy required.

3. Active systemic infections, coagulation disorders or other active major medical
illnesses of the cardiovascular, respiratory or immune system, as evidenced by a
positive stress thallium or comparable test, myocardial infarction, cardiac
arrhythmias, obstructive or restrictive pulmonary disease.

4. Advanced primary with impeding occlusion, perforation or bleeding, dependant on
transfusion.

5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
Disease and AIDS).

6. Concurrent opportunistic infections (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who have decreased immune
competence may be less responsive to the experimental treatment and more susceptible
to its toxicities.)

7. History of severe immediate hypersensitivity reaction to any of the agents used in
this study.

8. History of coronary revascularization or ischemic symptoms.

9. Any patient known to have an LVEF less than or equal to 45%.

10. Documented LVEF of less than or equal to 45% tested in patients with:

- Clinically significant atrial and/or ventricular arrhythmias including but not
limited to: atrial fibrillation, ventricular tachycardia, second or third degree
heart block

- Age greater than or equal to 60 years old

11. Documented FEV1 less than or equal to 60% predicted tested in patients with:

- A prolonged history of cigarette smoking.

- Symptoms of respiratory dysfunction.

12. Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with
known underlying liver dysfunction.