Study of Treatment for HPV16+ ASC-US or LSIL
Study of Treatment for HPV16+ ASC-US or LSIL
Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein
 vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine
Primary Objectives

 1. To determine the safety and feasibility of intra-muscular administration of
 pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL.

 2. To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA
 vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical
 trial.

 3. To determine the safety and feasibility of intra-muscular administration of
 pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with
 persistent HPV16+ ASC-US/LSIL.
Inclusion Criteria:

 1. Patients with persistent (>6 month period) ASC-US/LSIL determined by cervical cytology
 at study entry (ThinPrep with imaging)

 2. Patients whose cytologic samples are persistent (>6 month period) HPV16+ by Roche
 Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV
 genotyping test at study entry. Co-infections with HPV types other than HPV16 are
 permissible for study entry.

 3. Age ≥ 19 years

 4. Baseline Eastern Cooperative Oncology Group

 5. Patients must have adequate organ function at the time of enrollment as defined by the
 following parameters:

 -  White blood cell count > 3,000

 -  Absolute lymphocyte number > 500

 -  Absolute neutrophil count > 1,000

 -  Platelets > 90,000

 -  Hemoglobulin > 9

 -  Total bilirubin <3 X the institutional limit of normal

 -  AST(SGOT)/ALT(SGPT) <3 X the institutional limit of normal

 -  Creatinine < 2.5X the institutional limit of normal

 6. Women of child-bearing potential must agree to use two forms of contraception
 (hormonal and barrier) prior to study entry and for 3 months after study completion.

 7. Ability to understand and the willingness to sign a written informed consent document.

 8. Subject is able to adhere to the study visit schedule and other protocol requirements.

 Exclusion Criteria:

 1. Patients with ASC-US/LSIL determined by cervical cytology at study entry that are
 HPV16 negative.

 2. Histologic evidence of CIN2+

 3. Patients with a diagnosis of immunosuppression or prolonged, active use of
 immunosuppressive medications such as steroids.

 4. Prior vaccination with any HPV antigen (prophylactic or therapeutic).

 5. Patients who are receiving any other investigational agents within 28 days prior to
 the first dose.

 6. Patients with an uncontrolled intercurrent illness including, but not limited to,
 ongoing or active infection, symptomatic congestive heart failure, unstable angina
 pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
 limit compliance with study requirements.

 7. Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of
 a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.

 8. Patients with a history of allergic reactions attributed to compounds used in agent
 preparation.

 9. Patients who are pregnant or breast feeding.

 10. Patient with active or chronic infection of HIV, HCV, or HBV.

 11. Patients who have had a prior LEEP or cervical conization procedure.

 12. History of prior malignancy permitted if patient has been disease free for ≥ 5 years;
 however individuals with completely resected basal cell or squamous cell carcinoma of
 the skin within this interval may be enrolled.

 13. Inability to understand or unwillingness to sign an informed consent document.