The goal of this study is to find out about the safety of injecting the gene (DNA) for mouse
TYRP2 in patients with melanoma. DNA is a material that contains the information needed to
produce many substances in the body. TYRP2 is a substance found in melanoma cells that helps
to produce their black color. The DNA used in this study is the gene for mouse TYRP2.
The gene is introduced into bacteria, which are grown in large quantities. The DNA vaccine
is then made from bacteria that is inactive.
We would like to see if we can immunize patients against TYRP2 by injecting mouse TYRP2 DNA.
We will also follow the patients closely to see if there are any side effects. Mouse TYRP2
DNA is very similar to human TYRP2 DNA. We believe, based on lab experiments, that injection
of mouse TYRP2 DNA could result in the production of immune substances (antibodies and T
cells) that recognize melanoma cells. Antibodies are substances produced by your immune
system to defend your body against bacteria and viruses. T cells are a type of white blood
cell that can also fight infections. The small differences between mouse and human TYRP2 may
allow your immune system to make the antibodies and T cells against melanoma. There is no
evidence yet that injection of TYRP2 DNA results in any clinical benefit in patients.
- For all patients, pathology slides must be reviewed by the Memorial Hospital
Department of Pathology for confirmation of melanoma diagnosis.
- Patients must be HLA-A*0201 positive.
- Patients must have a Karnofsky performance status of at least 80.
- Patients must be free of detectable brain metastases.
- Patients must have adequate organ and marrow function as defined below:
- WBC ≥ than or = to 3,000/μL
- Absolute neutrophil count ≥ than or = to 1,500/μL
- Platelets ≥ than or = to 100,000/μL
- Total bilirubin ≤ than or = to 1.5X upper normal institutional limits
- LDH ≤ than or = to 2 X institutional upper limit of normal
- Albumin ≥ than or = to 3.5 mg/dl
- Creatinine ≤ than or = to 2.0 mg/dl
- Hemoglobin ≥ than or = to 10 Gm/dl
- Liver AST, ALT ≤ than or = to 2.5 x ULN
- Patients must have no known HIV positivity
- Pediatric patients are eligible if weight is > 25 kg and parent/guardian completes
informed assent process.
- Patients must understand and sign an informed consent and have specifically declined
all standard or approved therapies for which they would be considered eligible.
Parent or legal guardians of patients who are minors will sign the informed consent
- As part of the consent process, patients must agree to use contraception while on
- Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks
prior to entering the study or those who have not recovered from adverse events due
to agents administered more than 4 weeks earlier. For nitrosoureas, at last six weeks
must have elapsed.
- Patients with Grade I fever, active infection, or antibiotics within 72 hours prior
- Patients who have previously been immunized with any class of vaccine containing
TYRP2, including whole cell, shed antigen or cell lysate vaccine.
- Patients with a history of collagen vascular, rheumatological, or other autoimmune
- Any medical condition or use of medication (e.g., corticosteroids) which might make
it difficult for the patient to complete the full course of treatments or to respond
immunologically to vaccines is grounds for exclusion, at the discretion of the
Principal Investigator or co-Principal Investigators.
- Patients who have preexisting retinal or choroidal eye disease.
- Patients with serious underlying medical conditions that could be exacerbated by
participation, active infections requiring antimicrobial drugs or active bleeding.
- Pregnant women or women who are nursing are not eligible. Women of child-bearing
potential and sexually active men must be using appropriate contraception during the
course of this study. Women of child-bearing potential must not be pregnant (negative
βHCG within 2 weeks of immunization) nor be nursing during treatment.
- Patients receiving other investigational agents.