A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD) +/-GMCSF

Inclusion Criteria:

- Patients must be at least 18 years of age with a histologic diagnosis of
adenocarcinoma of the prostate.

- Patients must have metastatic prostate cancer (clinical stage D1 or D2 disease), with
previously documented lymph node, soft tissue and/or bone metastases by radiographic
imaging (including CT (or MRI) of abdomen and pelvis and bone scintigraphy). Patients
in situations in which there is a reasonable clinical suspicion of a second primary
tumor (or other non-prostate cancer reason for radiographic abnormalities) are not
eligible unless metastatic disease is histologically confirmed to be prostate cancer.

- Patients must have started androgen deprivation therapy (bilateral orchiectomy versus
LHRH agonist, and with or without androgen antagonist) at least one month (4 weeks)
prior to enrollment and no more than six months (24 weeks) prior to enrollment.
Patients must continue the androgen deprivation therapy throughout the study period,
and patients are not permitted to change the type of androgen deprivation therapy
(e.g. by adding an androgen antagonist) during the course of investigational therapy.

- Patients must have a serum testosterone < 50 ng/dL demonstrated within 1 month of
study entry.

- Patients must either not be a candidate for docetaxel chemotherapy for newly diagnosed
metastatic prostate cancer, as determined by their treating oncologist, or have
declined this therapy

- Patients must have evidence of response to androgen deprivation as defined by a
documented decline in serum PSA values from pre-androgen deprivation treatment
baseline and without evidence of PSA progression while on androgen deprivation
(defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of
2 ng/mL over nadir).

- Patients with a prior history of a second malignancy are eligible provided they have
been treated with curative intent and have been free of disease greater than three
years. There will be no exclusion for patients with a history of basal cell carcinoma,
squamous cell skin cancer, or other in situ carcinoma that has been adequately
treated.

- Patients who are sexually active must use a reliable form of contraception while on
study and for 4 weeks after the last immunization.

- ECOG performance score < 2.

- Patients must have adequate hematologic, renal and liver function as defined by: WBC >
3000/mm3, hematocrit > 30%, platelet count > 100,000/mm3, serum creatinine < 1.6 mg/dl
or a calculated creatinine clearance > 60 cc/min, and serum bilirubin < 2.0 mg/dl,
within 4 weeks prior to first immunization.

- Patients must be informed of the experimental nature of the study and its potential
risks and must sign an IRB-approved written informed consent form indicating such an
understanding.

Exclusion Criteria:

- Small cell or other (non-adenocarcinoma) variant prostate cancer histology.

- Patients cannot have evidence of immunosuppression or have been treated with
immunosuppressive therapy, such as chemotherapy, chronic treatment dose
corticosteroids (greater than the equivalent of 10 mg prednisone per day), or
radiation therapy to >30% of the bone marrow, within 6 months of the first
vaccination. Treatment or salvage radiation therapy encompassing < 30% of bone marrow
must have been completed 4 weeks prior to the first vaccination.

- Seropositive for HIV, hepatitis B (HBV) or hepatitis C (HCV) per patient history.

- Patients previously treated with neoadjuvant and/or adjuvant androgen deprivation
(e.g. with radiation therapy) prior to the 6-month eligibility period are allowed,
assuming they did not meet criteria for progression (defined by PCWG2 criteria as a
25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir) while on
treatment.

- Patients must not be concurrently taking other medications or supplements with known
hormonal effects (other than LHRH agonists or non-steroidal anti-androgen), including
PC-SPES, megestrol acetate, finasteride, ketoconazole, estradiol, or Saw Palmetto. All
other medications with possible anti-cancer effects must be discussed with the
Protocol Principal Investigator prior to study entry.

- Patients previously treated with herbal supplements as described in 6.B.5, or other
potential or experimental therapies for prostate cancer (apart from LHRH agonists and
antiandrogens as described in 6.A.3 above), must have been discontinued these
treatments and completed at least a one-month washout prior to first vaccination.

- Patients must not have plans to receive concomitant chemotherapy, other biological or
immune therapies, or radiation therapy for the treatment of prostate cancer during the
period of study treatment.

- Patients must not have known psychological or sociological conditions, addictive
disorders or family problems, which would preclude compliance with the protocol.

- Patients must not have known allergic reactions to GM-CSF or the tetanus vaccine.

- Prior treatment with another experimental anti-tumor vaccine is permissible.

- Patients with unstable or severe intercurrent medical conditions or laboratory
abnormalities that would impart, in the judgment of the Protocol Principal
Investigator, excess risk associated with study participation or study agent
administration.

- Unable or unwilling to undergo two leukapheresis procedures.

- Patients with medical conditions precluding leukapheresis.

- Patients cannot have concurrent enrollment on other phase I, II, or III
investigational treatment studies for the treatment of prostate cancer.