E7 TCR T Cells for Human Papillomavirus-Associated Cancers

• INCLUSION CRITERIA:

1. Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by insitu hybridization (ISH) or a polymerase chain reaction (PCR)-based test).

2. Patients must be HLA-A02 by low resolution typing, and HLA-A02:01 by one ofthe high resolution type results.

3. All patients must have received prior first line standard therapy or declinedstandard therapy.

4. Patients with three or fewer brain metastases that have been treated withsurgery or stereotactic radiosurgery are eligible. Lesions that have beentreated with stereotactic radiosurgery must be clinically stable for one monthbefore protocol treatment. Patients with surgically resected brain metastasesare eligible.

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

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

7. Clinical performance status of ECOG 0 or 1.

8. Individuals must be willing to practice birth control from the time ofenrollment on this study up to twelve (12) months after treatment. Individualsmust be willing to undergo testing for HPV-16 prior to becoming pregnant afterthis period.

9. Individuals of childbearing potential must have a negative pregnancy testbecause of the potentially dangerous effects of the treatment on the fetus.Individuals of childbearing potential are defined as all individuals exceptindividuals who are postmenopausal or who have had a hysterectomy.Postmenopausal will be defined as individuals over the age of 55 who have nothad a menstrual period in at least one year. Because there is a potential riskfor adverse events in nursing infants secondary to treatment of the mother withE7 TCR transduced PBL, breastfeeding should be discontinued if the individualis treated with E7 TCR transduced PBL. These potential risks may also apply toother agents used in this study.

10. Serology:

• Seronegative for HIV antibody. (The experimental treatment being evaluated in thisprotocol depends on an intact immune system. Patients who are HIV seropositive canhave decreased immune-competence and thus are less responsive to the experimentaltreatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. Ifhepatitis C antibody test is positive, then the patient must be tested for thepresence of antigen by RT-PCR and be HCV RNA negative. a. Hematology:

• Absolute neutrophil count greater than 1000/mm^3 without the support of

filgrastim.

• WBC greater than or equal to 3000/mm^3

• Platelet count greater than or equal to 100,000/mm^3

• Hemoglobin > 8.0 g/dL b. Chemistry:

• Serum ALT/AST less than or equal to 2.5 times the upper limit of normal

• Calculated creatinine clearance (CCr) greater than or equal to 50 mL/min/1.73^2using the Cockcroft-Gault equation

• Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert'sSyndrome who must have a total bilirubin less than 3.0 mg/dL c. More than four weeks must have elapsed since any prior systemic therapy at thetime the patient receives the E7 TCR cells.

Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less.

EXCLUSION CRITERIA:

1. Active systemic infections (for e.g.: requiring anti-infective treatment),coagulation disorders or other active major medical illnesses of the cardiovascular,respiratory or immune system, as evidenced by a positive stress thallium orcomparable test, myocardial infarction, cardiac arrhythmias, severe obstructive orrestrictive pulmonary disease. Patients with abnormal pulmonary function tests butstable obstructive or restrictive pulmonary disease may be eligible.

2. Any form of primary immunodeficiency (such as Severe Combined ImmunodeficiencyDisease).

3. Concurrent opportunistic infections (The experimental treatment being evaluated inthis protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptibleto its toxicities).

4. Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis,rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupuserythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are notexclusionary.

5. Patients on immunosuppressive drugs including corticosteroids. With the exceptionof: intranasal, inhaled, topical steroids, or local steroid injection (e.g.,intra-articular injection)

-Systemic corticosteroids at physiologic doses 10 mg/day of prednisone orequivalent; or,

-Steroids as premedication for hypersensitivity reactions (e.g., CT scanpremedication)

6. History of severe immediate hypersensitivity reaction to cyclophosphamide,fludarabine or aldesleukin.

7. Patients with a history of coronary revascularization or ischemic symptoms unlesspatient has a normal cardiac stress test.

8. Documented LVEF of less than or equal to 45% tested. The following patients willundergo cardiac evaluations

9. Clinically significant atrial and/or ventricular arrhythmias including but notlimited to: atrial fibrillation, ventricular tachycardia, second or thirddegree heart block or

10. Age greater than or equal to 50 years old

11. Any other condition, which would, in the opinion of the Principal Investigator,indicate that the subject is a poor candidate for the clinical trial or wouldjeopardize the subject or the integrity of the data obtained.

12. Subjects with baseline screening pulse oxygen level of < 95% on room air will not beeligible. If the underlying cause of hypoxia improves, then they may be reevaluated