CISH Inactivated Tumor-Infiltrating Lymphocytes for the Treatment of Metastatic Gastrointestinal Epithelial Cancer

Inclusion Criteria

• Diagnosis of metastatic gastrointestinal epithelial cancer with progressive disease following at least one first line standard therapy. Prior investigational therapy must be discussed with and approved by the study principal investigator (PI) (Dr. Lou).When available, archived tissue from original diagnosis will be obtained for research related testing
• Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with at least one lesion identified as resectable for TIL generation (minimum volume of tumor tissue required is 1 cm^2 as single mass or fragments) and at least one other lesion meeting the RECIST criteria for measurable to serve as an indicator of disease response. The location of the tumor for TIL generation and method used to obtain (i.e. laparoscopy, endoscopic ultra sound, etc.) will be determined based on an individual patient’s disease
• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. Patients must not be receiving systemic steroids. Brain metastases are assessed using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Serology testing within 3 months of study enrollment (tumor collection): * Seronegative for human immunodeficiency virus (HIV) antibody. (The investigational 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 study treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcriptase polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative. * Seronegative for hepatitis B virus core antibody (anti-HBc), hepatitis B virus (HBV)/HCV/HIV-1 nucleic acid testing (NAT), human T-lymphotropic virus-I/II antibody (anti-HTLV-I/II), Trypanosoma cruzi antibody (anti-T. cruzi), West Nile virus NAT, Cytomegalovirus antibody (anti-CMV), and rapid plasma reagin (RPR). (Note: Other blood viral testing may be required as updated on the Food and Drug Administration [FDA] website: https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm09 5440.htm#approved).
• Absolute neutrophil count > 1000/mm^3 without the support of filgrastim (within 14 days of study enrollment)
• White blood cell (WBC) >= 3000/mm^3 (within 14 days of study enrollment)
• Platelet count >= 75,000/mm^3 (within 14 days of study enrollment)
• Hemoglobin > 8.0 g/dl (within 14 days of study enrollment). Subjects may be transfused to reach this cut-off
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5.0 x upper limit of normal (ULN) (within 14 days of study enrollment)
• Serum creatinine =< 1.6 mg/dl (within 14 days of study enrollment)
• Total bilirubin =< to 2.0 mg/dl, except in patients with Gilbert’s Syndrome, who must have a total bilirubin =< 3.0 mg/dl (within 14 days of study enrollment)
• Willing to undergo outpatient non-mobilized leukapheresis (3 hour collection) in association with the tumor collection
• Agrees to remain in the Twin Cities metropolitan area (within 1 hour drive of the University of Minnesota) after the CISH KO TILs infusion through the end of treatment visit (~ day 28)
• Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria

• Pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. Women of childbearing potential (defined as menses within previous 12 month and/or follicle stimulating hormone [FSH] =< 40 IU/L) must have a negative pregnancy test (serum or urine) within 7 days of enrollment
• Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
• Prior treatment with any cell therapy product
• Concurrent opportunistic infection (The treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the treatment and more susceptible to its toxicities)
• Active systemic infections requiring anti-infective treatment, coagulation disorders or any other active major medical illnesses
• Use of systemic steroids (0 mg) within 14 days or more days prior to tumor collection and TIL harvest or use of systemic steroids (0 mg) within 21 days or more days prior to TIL Infusion
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, aldesleukin, or dimethyl sulfoxide (DMSO)
• History of coronary revascularization or ischemic symptoms
• Documented left ventricular ejection fraction (LVEF) =< 45% tested in patients age >= 65 years and/or with clinically significant atrial and/or ventricular arrhythmias, including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block, or have a history of ischemic heart disease and/or chest pain. Patients < 65 years of age who present with cardiac risk factors (e.g., diabetes, hypertension, obesity) may undergo cardiac evaluation as noted above
• Clinically significant patient history that, in the judgment of the PI, would compromise the patient’s ability to tolerate high-dose aldesleukin
• Documented forced expiratory volume in 1 second (FEV1) =< 50% predicted tested in patients with: * A prolonged history of cigarette smoking (approximately 20 packs/year within the past 2 years) and/or * Symptoms of respiratory dysfunction
• Receiving any investigational agents
• Medical status or social situation that may make study participation not in the best interest of the patient in the opinion of the enrolling investigator