Humoral response to a viral glycan correlates with survival on PROSTVAC-VF.

Abstract:

:Therapeutic cancer vaccines can be effective for treating patients, but clinical responses vary considerably from patient to patient. Early indicators of a favorable response are crucial for making individualized treatment decisions and advancing vaccine design, but no validated biomarkers are currently available. In this study, we used glycan microarrays to profile antiglycan antibody responses induced by PROSTVAC-VF, a poxvirus-based cancer vaccine currently in phase III clinical trials. Although the vaccine is designed to induce T-cell responses to prostate-specific antigen, we demonstrate that this vaccine also induces humoral responses to a carbohydrate on the poxvirus, the Forssman disaccharide (GalNAcα1-3GalNAcβ). These responses had a statistically significant correlation with overall survival in two independent sample sets (P = 0.015 and 0.008) comprising more than 100 patients. Additionally, anti-Forssman humoral responses correlated with clinical outcome in a separate study of PROSTVAC-VF combined with a radiopharmaceutical (Quadramet). Studies on control subjects demonstrated that the survival correlation was specific to the vaccine. The results provide evidence that antiglycan antibody responses may serve as early biomarkers of a favorable response to PROSTVAC-VF and offer unique insights for improving vaccine design.

authors

Campbell CT,Gulley JL,Oyelaran O,Hodge JW,Schlom J,Gildersleeve JC

doi

10.1073/pnas.1314722111

subject

Has Abstract

pub_date

2014-04-29 00:00:00

pages

E1749-58

issue

17

eissn

0027-8424

issn

1091-6490

pii

1314722111

journal_volume

111

pub_type

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