Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: clinical and immunological results.
MDA-MB-231, an HLA-A2(+), HER2/neu(+) allogeneic breast cancer cell line genetically modified to express the costimulatory molecule CD80 (B7-1), was used to vaccinate 30 women with previously treated stage IV breast cancer. Expression of CD80 conferred the ability to deliver a costimulatory signal and thereby improved the antigen presentation capability of the tumor cells to patient T cells in vitro. Patients were vaccinated with 10(7) or 10(8) irradiated gene-modified tumor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or BCG, three times at 2-week intervals and then monthly until progressive disease developed. GM-CSF-related flulike symptoms and minor injection site reactions were observed frequently. Prolonged disease stabilization was observed in four patients but no objective tumor regressions were seen. Immune responses were measured in matched peripheral blood samples collected before and after treatment from 9 of 15 patients treated at the 10(8) tumor cell dose. Four patients exhibited MHC class I-restricted cytokine production in response to the parental breast cancer cell line. One patient maintained an increased number of circulating tumor-specific, interferon gamma-secreting CD8(+) T cells for 24 months after the last vaccination. One patient exhibited a tumor-specific interleukin 5 response to an autologous tumor cell line. This immunization strategy proved to be safe and feasible, and induced tumor-specific immune responses in a minority of patients; however, no objective tumor regressions were observed.
Dols
Annemieke
A
Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213, USA.
Smith
John W
JW
Meijer
Sybren L
SL
Fox
Bernard A
BA
Hu
Hong-Ming
HM
Walker
Edwin
E
Rosenheim
Sidney
S
Moudgil
Tarsem
T
Doran
Teri
T
Wood
William
W
Seligman
Mark
M
Alvord
W Gregory
WG
Schoof
Deric
D
Urba
Walter J
WJ
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D003115:Colony-Stimulating Factors / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D003115:Colony-Stimulating Factors; D016207:Cytokines; D015789:HLA-A2 Antigen; D007519:Isoantigens