SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer

This is a single arm, open label study of SV-BR-1-GM in recurrent and/or metastatic breast
cancer. The detailed treatment regimen follows:

Pre-Inoculation Regimen:

Cyclophosphamide (Cytoxan) 300 mg/m^2 I.V., 1x only, will be given 48-72 hours before each
SV-BR-1-GM inoculation, with an antiemetic of the provider's choice (steroids prohibited). If
the patient is not tolerating the cyclophosphamide, a lower dose may be used (e.g. 200 or 150
mg/m^2) or it may be withheld, with the Sponsor's approval.

Innoculation Day Standard Operating Procedures:

1. Inquire regarding events of past weeks, change in medications, pain scale, ECOG scale,
and review of systems.

2. Check injection sites.

3. Perform DTH skin test intra-dermally with the SV-BR-1 parent cell line (~1 x 10^6
irradiated tumor cells). Observe about 20 minutes for acute hypersensitivity. Grade III
or higher acute hypersensitivity will abort therapy.

4. Inject SV-BR-1-GM intra-dermally into 4 sites in thighs and upper back (0.5 mL each).
Monitor patients for 60 minutes. Vital signs will be assessed and medical attention will
be warranted if unstable.

SV-BR-1-GM Preparation & Inoculation Regimen:

Each inoculation will be administered via intra-dermal injection at the investigational
sites. Subjects will receive 15-25 x 10^6 viable, irradiated transfected breast tumor cells
in a total volume of 2.0 ml Ringer's lactate. SV-BR-1-GM cells will be irradiated to ensure
cell replication incompetency.

SV-BR-1-GM will be divided into four aliquots of 0.5 mL each and injected intra-dermally; one
each into the anterior skin of the subject's right and left thighs and over the right and
left upper back . Application of anesthetic lidocaine crème may be used if necessary for
control of local pain before inoculation. Subjects will be monitored for 60 minutes.

After at least 10 subjects have been treated safely with this regimen, the dose of SV-BR-1-GM
may be escalated or decreased in subsequent patients based on the emerging data.

Post-Inoculation Regimen:

2 days (± 1 day) after inoculation, and again 4 days (± 1 day) later after inoculation, the
patient will return to the principal investigator's office to receive Interferon-alpha-2b
(Merck) in 0.1 mL saline, prepared as follows: These will also be provided by the sponsor and
injected intra-dermally to each inoculation site, beneath the thickest area. Again, subjects
will be observed about 20 minutes. The DTH response will also be recorded at the 2 days (± 1
day) visit.

This cycle will be performed every 2 weeks for the first month of treatment (3 inoculations),
and then every month for up to one year.

Inclusion Criteria:

- 1. Have histological confirmation of breast cancer with recurrent and/or metastatic
lesions via investigational site.

- Patients with new or progressive breast cancer metastatic to brain will be
eligible provided:

1. There is no need for steroids and patients have not had steroids at least 2
weeks

2. No individual tumor size is >50 mm3

3. ECOG status <3

4. Tumor is not impinging on Middle Cerebral Artery/speech-motor strip

5. If surgically debulked, must be healed from surgery and at least 3 weeks
have elapsed since general anesthesia

6. Patients consent to MRI studies at 3-4 week intervals until evidence of
tumor regression on at least 2 imaging studies. In no case, will the
interval between MRI studies be longer than 3 months. MRI study may be
introduced at any time should the patients develop new or clearly worsening
symptoms and/or introduction of steroids

2. Have evidence of persistent, recurrent, or progressive disease for which
there is no known or established treatment available with curative intent,
after failing at least one course of community standard systemic treatment
with chemotherapy (and endocrine therapy if appropriate)

3. Be 18 years of age or older and female

4. Have expected survival of at least 4 months

5. Have adequate performance status (ECOG 0-2)

6. Patients may be maintained on hormonal therapy provided there is clear
evidence of tumor progression

7. Have provided written informed consent.

Exclusion Criteria:

1. Concurrent or recent chemotherapy (within 3 weeks), XRT within 3 weeks, may have
had immunotherapy in the past (off within 3 weeks), or general anesthesia/major
surgery (within 3 weeks). Patients must have recovered from all known or expected
toxicities from previous treatment and passed a treatment-free "washout" period
of 3 weeks before starting this program (8 weeks for persons receiving
nitrosourea or mitomycin).

2. History of clinical hypersensitivity to GM-CSF, Interferon-alpha-2b (Merck),
yeast, beef, or to any components used in the preparation of the experimental
vaccine.

3. BUN >30 and a creatinine >2.

4. Absolute granulocyte count < 1000; platelets <100,000.

5. Bilirubin >2.0; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >2x
ULN.

6. Proteinuria >1+ on urinalysis or >1 gm/24hr.

7. Left ventricular ejection fraction (LVEF as determined by cardiac echo or MUGA
scan) below the normal limits of the institutions specific testing range. This
assessment may be repeated once at the discretion of the Investigator with the
approval of the Sponsor.

8. New York Heart Association stage 3 or 4 cardiac disease.

9. A pleural effusion of moderate severity or worse.

10. Any woman of childbearing potential, unless she:

1. Agrees to take measures to avoid becoming pregnant during the study and

2. Has a negative serum pregnancy test within 7 days prior to starting
treatment.

11. Women who are pregnant or nursing.

12. Patients with concurrent second malignancy. Persons with previous malignancies
effectively treated and not requiring treatment for >24 months are eligible,
provided there is unambiguous documentation that current local recurrence or
metastatic site represents recurrence of the primary breast malignancy.

13. Patients who are HIV positive (by self-report) or have clinical or laboratory
features indicative of AIDS.

14. 14. Patients who require systemic steroids at a dose equivalent of >10 mg/day of
prednisone. Beta-blocker therapy, while not exclusionary, is discouraged and
alternatives should be sought if possible. The beta-blocker might compromise use
of epinephrine for the rare possibility of anaphylaxis. Anticoagulants must be
approved by the Investigator with notification of the Sponsor.

15. Patients who are on treatment for rheumatological or autoimmune disease unless
approved by the Investigator in consultation with the Sponsor (e.g., as for
replacement therapy for autoimmune thyroiditis or diabetes).

16. Patients with severe psychiatric (i.e. schizophrenia, bipolar, or borderline
personality disorder) or other clinically progressive major medical problems,
unless approved by the PI.

17. Male breast cancer patients.

18. Patients may not be on a concurrent clinical trial, unless approved by PI.