Non-Viral TCR Gene Therapy

* INCLUSION CRITERIA:
* Patients with histologically confirmed solid cancer that falls into one of four cohorts:

  * Gastrointestinal and genitourinary (Cohort 1),
  * Breast and ovarian (Cohort 2),
  * Non-small cell lung cancer (NSCLC), NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas (Cohort 3),
  * Glioblastoma (Cohort 4)
* Patients must have evaluable or measurable disease per RECIST 1.1 with at least one lesion that is resectable for TIL generation with minimal morbidity plus at least one other lesion that can be measured. Metastatic disease is required for Cohorts 1-3 but is not required for Cohort 4.
* Patients must have:

  * previously received standard systemic therapy for their advanced cancer and have been either non-responders or have recurred, specifically:

    * Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan (or similar agents)
    * Patients with breast and ovarian cancer must be refractory to first-line treatments
    * Patients with lung cancer must have received at least one platinum-based chemotherapy regimen and at least one FDA-approved targeted treatment (when appropriate)
    * Patients with glioblastoma must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered NED). This includes recurrent GBM after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro- anatomical considerations) and adjuvant radiotherapy +/- chemotherapy. OR
  * declined standard treatment
* For Cohorts 1-3: Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
* For Cohort 3: Patients must have documented FEV1 \> 60% predicted.
* Age greater than or equal to 18 years and less than or equal to 70 years.
* For Cohorts 1-3: Clinical performance status of ECOG 0 or 1.
* For Cohort 4: Patients must have Karnofsky performance status of greater than or equal to 60.
* The effects of study treatment on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at time of study entry, for the duration of treatment and up to 4 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* 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.
* Hematology

  * ANC \> 1,000/mm\^3 without the support of filgrastim
  * WBC greater than or equal to 3,000/mm\^3
  * Platelet count greater than or equal to 100,000/mm\^3
  * Hemoglobin \> 8.0 g/dL. Subjects may be transfused to reach this cut-off.
* Chemistry

  * Serum ALTlAST less than or equal to 5.0 x ULN
  * Serum creatinine less than or equal to 1.6 mgldL
  * Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL.
* More than four weeks must have elapsed since completion of any prior systemic therapy and enrollment.

Note: Patients may have undergone minor surgical procedures or limited field radiotherapy (with the exception of patients with glioblastoma) within the four weeks before enrollment, as long as any related major organ toxicities have recovered to less than or equal to grade 1.

* For Cohort 3: More than two weeks must have elapsed since any prior palliation for major bronchial occlusion or bleeding and enrollment, and patient s toxicities must have recovered to less than or equal to grade 1.
* For Cohort 4: Patients must be at least four weeks from radiation therapy. Additionally, patients must be at least six weeks from nitrosoureas, four weeks from temozolomide, three weeks from procarbazine, two weeks from vincristine and four weeks from last bevacizumab administration. Patients must be at least four weeks from other cytotoxic therapies not listed above and two weeks for non-cytotoxic agents (e.g., interferon) including investigative agents. Patient s toxicities must have recovered to less than or equal to grade 1.
* Ability of subject to understand and the willingness to sign a written informed consent document.
* Willing to sign a durable power of attorney.
* Subjects must be co-enrolled on protocol 03-C-0277.

EXCLUSION CRITERIA:

* Pregnant women are excluded from this study because study treatment s potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated on this trial.
* Concurrent systemic steroid therapy, except for patients with glioblastoma (Cohort 4).
* Active systemic infections requiring anti-infective treatment, coagulation disorders or any other active or uncompensated major medical illnesses.
* For Cohort 3: Any major bronchial occlusion or bleeding not amenable to palliation.
* For Cohort 4: Clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding six months that were not related to glioma surgery.

Note: History of prior intratumoral bleeding is not an exclusion criterion; however, patients with a history of prior intratumoral bleeding will need to undergo a non- contrast head CT to exclude acute bleeding.

* 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.)
* History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
* History of coronary revascularization or ischemic symptoms.
* Documented LVEF less than or equal to 45% tested in patients:

  * Age greater than or equal to 65 years
  * 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.
* Documented FEVl less than or equal to 50% predicted tested in patients with:

  * A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history within the past two years).
  * Symptoms of respiratory dysfunction.
* Clinically significant patient history which in the judgment of the Principal Investigator (PI) would compromise the patients ability to tolerate high-dose aldesleukin.
* Patients who are receiving any other investigational agents.