Serum antibodies to blood group A predict survival on PROSTVAC-VF.
OBJECTIVE
There is evidence that therapeutic cancer vaccines can lengthen survival for some patients with cancer, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy.


METHODS
This retrospective study included 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus-based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. A glycan microarray was used to profile prevaccination antiglycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. The screen for predictive biomarkers identified antiglycan antibodies that consistently stratified subjects into groups with different Kaplan-Meier survival estimates. Because of the potential for overfitting, a permutation test was used to estimate the false discovery rate.


RESULTS
Prevaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri immunoglobulin M (IgM) relative to subjects with little or no preexisting IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate-specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival.


CONCLUSIONS
In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the use of glycan microarray technology for improving our understanding of vaccine immunology. Clin Cancer Res; 19(5); 1290-9. ©2012 AACR.
Chemical Biology Laboratory, National Cancer Institute, NIH, Frederick, Maryland 21702, USA.
Christopher T
CT
Campbell
James L
JL
Gulley
Oyindasola
O
Oyelaran
James W
JW
Hodge
Jeffrey
J
Schlom
Jeffrey C
JC
Gildersleeve
D000017:ABO Blood-Group System / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000097:blood; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016022:Case-Control Studies; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005500:Follow-Up Studies; D005822:Genetic Vectors / Q000008:administration & dosage*; D006031:Glycosylation; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D015996:Survival Rate; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D054928:Validation Studies as Topic
D000017:ABO Blood-Group System; D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D011134:Polysaccharides; D014614:Vaccines, Synthetic; D017430:Prostate-Specific Antigen