A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
Background: T cell based adoptive immunotherapy including CTL and TIL may stimulated the
 immune system and stop cancer cells from growing.

 Objective: Phase I clinical trial to investigate the toxicity and immune response of therapy
 with autologous tumor infiltrating lymphocytes as adjuvant treatment for metastatic
 nasopharyngeal carcinoma and hepatocellular carcinoma after primary operation, radiotherapy
 and chemotherapy.

 Methodology: Phase I clinical trial in patients with advanced nasopharyngeal carcinoma,
 hepatocellular carcinoma, breast cancer and other solid cancers. The investigators isolated
 lymphocytes from fresh tumor tissues, activated and expanded TILs in vitro; and infused the
 enough number (10e9 to 10e10) of TIL back patients.
Tumor infiltrating lymphocytes were isolated from tumor tissues from tumor biopsy or
 operation. These TILs were cultured in human IL-2 medium for 2 to 3 weeks, and reactivated by
 OKT3, irradiated feeder cells from the PBMCs of healthy donors and LCL set from
 EBV-transformed normal B cells, and expanded in human IL-2 medium for another 15 days. 10e9
 to 10e10 TILs were yielded. The phenotype, function and sterile were detected before these
 TILs infused patients. After accepting operation or first round of routine chemotherapy and
 radiotherapy, the patients were treated with autologous TILs 10e9-10e10 via intravenous in 30
 min, q weekX2 weeks, and followed by two weeks with daily sc low-dose interleukine-2.

 Patients will be evaluated for toxicity and immune response. Peripheral blood of patients
 using multimer analysis and/or ELISPOT assays. Additional, we will be able to determine
 anti-tumor effects from immunotherapy by evaluating the clinical response of patients with
 stable or progressive disease at the time of TILs infusion. Lastly, we will assess additional
 tumor markers in patients with relapsed/refractory disease by immunohistochemical staining of
 tumor sections from previous diagnostic or therapeutic biopsy samples to determine the
 incidence of additional tumor antigen targets that may be used in future studies.
Inclusion Criteria:

 -  Patients with nasopharyngeal carcinoma in stage IVa or Ivb and patients with
 metastatic hepatocellular carcinoma were planned for tumor biopsy or primary surgeon

 -  Age 18 to 70 years.

 -  Willing to sign a durable power of attorney

 -  Able to understand and sign the Informed Consent Document

 -  Life expectancy of greater than three months

 -  Patients of both genders must be willing to practice birth control from the time of
 enrollment on this study and for up to four months after receiving the preparative
 regimen.

 -  Serology:

 -  Seronegative for HIV antibody.

 -  Women of child-bearing potential must have a negative pregnancy test because of
 the potentially dangerous effects of the preparative chemotherapy on the fetus.

 -  Hematology:

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

 -  Platelet count greater than 100,000/mm.

 -  Hemoglobin greater than 8.0 g/dl.

 -  Chemistry:

 -  Serum ALT/AST less or equal to 2.5 times the upper limit of normal.

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

 -  Total bilirubin less than or equal to 1.5 mg/dl, except in patients with
 Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

 Exclusion Criteria:

 -  Previous treatment with IL-12.

 -  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.

 -  Active systemic infections, coagulation disorders or other major medical illnesses of
 the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
 arrhythmias, obstructive or restrictive pulmonary disease.

 -  Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
 Disease).

 -  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).

 -  Concurrent systemic steroid therapy.