Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogeneic tumor cells.
Thirty HLA-A2 women with metastatic breast cancer received up to 14 vaccinations with MDA-MB-231-CD80, an HLA-A2 allogeneic breast cancer cell line, which had been lipofected with the cDNA for the CD80 costimulatory molecule. Tumor cells were administered with BCG or GM-CSF as an adjuvant. Sera obtained before and after vaccination were analyzed for antibodies to tumor cell lysate, MUC1, HER2/neu and p53. Since the cell line was grown in fetal bovine serum (FBS), sera were also analyzed for antibodies to FBS. Eighteen of 24 patients for whom sera were available exhibited anti-FBS activity at baseline. Eleven of these 18 patients and all six patients without baseline anti-FBS activity showed an increased titer after vaccination. The anti-FBS activity required that serum samples be absorbed in excess FBS to detect specific antibodies to tumor cell lysate. A two-fold increase in the titer of IgG specific to tumor cell lysate was observed in 6 patients. Eight of 24 patients made an antibody response to HER-2/neu, four of 24 to MUC1 and one of 24 to p53. Although antibody production to a variety of tumor cell-associated antigens was detected our results suggest that a whole cell vaccine comprising a CD80-transfected allogeneic breast cancer cell line with adjuvant BCG or GM-CSF was not a reliable method to induce significant antibody responses in women with advanced breast cancer.
Dols
Annemieke
A
Robert W. Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA.
Meijer
Sybren L
SL
Hu
Hong-Ming
HM
Goodell
Vivian
V
Disis
Mary L
ML
Von Mensdorff-Pouilly
Silvia
S
Verheijen
Rene
R
Alvord
W Gregory
WG
Smith
John W
JW
Urba
Walter J
WJ
Fox
Bernard A
BA
D000368:Aged; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D015789:HLA-A2 Antigen / Q000097:blood; D006801:Humans; D007104:Immune Adherence Reaction; D007167:Immunotherapy / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015789:HLA-A2 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53