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1783
Vaccination of Breast Cancer Patients with a
Tumor Cell Vaccine Genetically Modified to Express the Costimulatory
Molecule, CD80. John Washburn Smith, Mark Seligman, Bernard A
Fox, Jill G Wood, Teri Doran, Lisa Justice, Annemiek M Dols, Sybren
L Meijer, Mary L Disis, William Wood, Walter J Urba, Earle A Chiles
Research Institute, Portland, OR; Univ of Washington, Seattle, WA;
Earle Chiles A Research Institute, Portland, OR.
Several animal studies have demonstrated that genetic alteration
of tumor cells with genes for costimulatory molecules leads to the
production of antigen-specific T cell responses that result in tumor
rejection. In an attempt to generate breast cancer specific immune
responses, HLA-A2+ patients (pts) with metastatic breast cancer were
vaccinated with the HLA-A2+, HER2+, CD54+ (ICAM-1), MDA-MB231
(MB231) allogeneic human breast cancer cell line transfected in
vitro with CD80 (B7.1) cDNA using lipofection techniques. Cohorts of
5 pts each received immunizations of 107 or 108
irradiated MDA-CD80 tumor cells given i.d. in the right thigh
every 2 wks x 3 then every month. In 4/6 cohorts, GM-CSF (Immunex)
was given s.c. every 12 hours for 7 days to stimulate dendritic
cells at either 50 mcg/m2 to the right and left anterior
thighs; or 125 mcg/m2 to the right thigh only. Two
cohorts received BCG alone as an adjuvant. Bilateral superficial
inguinal lymph nodes were removed on day 10 for immunologic testing.
Pt characteristics: median age-52, KPS-100, prior chemotherapy for
metastatic disease-50%, HER2 overexpression-50%. Of 27 evaluable
pts, 16 progressed at 2 mos and 11 had stable disease (SD). Ten pts
had SD at 4 mos and continued treatment for a total of 5-12 mos. No
objective responses occurred but one pt had a decrease in the CA15-3
tumor marker. Immunological testing has not been completed, but the
following preliminary results demonstrate the induction of an immune
response in many pts. Pre and post DTH skin testing (8pts) showed
induction of response (4pts) to the wild type MB231 as well as the
MDA-CD80. An anti-HER2 IgG response was induced or boosted in 1/3 of
the first 15 pts. Breast cancer-specific T-cell responses were
greater in the lymph nodes draining the tumor vaccine site compared
to the GM-CSF alone site. CTL activity against a p53 mutation
present in MB231 was demonstrated post-vaccination. We conclude that
an immunization strategy using a breast cancer cell line genetically
modified to express costimulatory molecules is feasible, safe and
capable of inducing breast cancer specific immune responses in pts
with advanced breast cancer.
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