NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine

To evaluate the safety of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine given by particle-mediated epidermal delivery (PMED) in patients with tumor types known to express NY-ESO-1 or LAGE-1.

NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 microgram dosage of NY-ESO-1 was administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage was administered as 8 X 1 microgram PMEDs. The third cohort of patients received the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day.

Blood samples were to be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients were to be evaluated for toxicity throughout the study.

Delayed-type hypersensitivity (DTH) testing was to be performed at baseline and at the 2-week visit following the first and third vaccinations.

NY-ESO-1 and/or LAGE-1 specific antibodies were to be assessed in all patients by an enzyme-linked immunosorbent assay (ELISA). NY-ESO-1 specific CD4+ and CD8+ T-cells were to be assessed in all patients by tetramer and/or ELISPOT assays.

Disease status was to be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease.

Eligibility Criteria:
Inclusion Criteria:

Patients were eligible for enrollment if they fulfilled all of the following criteria:

1. Histologically proven tumor type known to express NY-ESO-1 or LAGE-1 (prostate cancer, breast cancer, bladder cancer, hepatocellular cancer, synovial sarcoma, leiomyosarcoma, head and neck, lung cancer, esophageal, ovarian, neuroblastoma); or NY-ESO-1 or LAGE-1 positive tumors determined by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry or expression of LAGE-1 by RT-PCR.
2. Advanced disease and have declined, delayed, failed or completed standard therapy.
3. Full recovery from surgery.
4. Expected survival of at least 6 months.
5. Karnofsky performance scale ≥ 60.
6. Adequate bone marrow, kidney, liver and immune functions.
7. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Clinically significant heart disease (NYHA Class III or IV).
2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders, clinically significant liver or renal insufficiency requiring treatment.
3. Patients with serious intercurrent illness, requiring hospitalization.
4. Known HIV, Hepatitis B or Hepatitis C positivity.
5. History of autoimmune diseases (e.g. SLE, scleroderma). Vitiligo is not an exclusion criterion.
6. Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or non-steroidal anti-inflammatory drugs. Specific COX-2 inhibitors are permitted. Low dose aspirin is permitted. Topical or inhalational steroids are permitted.
7. Evidence of skin disease (e.g. psoriasis, eczema or keloid formation) at the proposed administration site.
8. Allergy to gold (including gold jewelry).
9. History or evidence of chrysotherapy (gold salts).
10. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas).
11. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer, cervical carcinoma in situ.
12. Mental impairment, in the opinion of the investigator, that may compromise the ability to give informed consent and comply with the requirements of the study.
13. Lack of availability for immunological and clinical follow-up assessments.
14. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
15. Pregnancy or breastfeeding.
16. Women of childbearing potential: Refusal or inability to use effective means of contraception.