Humoral responses to glycans as biomarkers of cancer vaccine efficacy

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-4

Authors

• C Campbell
• Y Zhang
• D Farnsworth
• J Gildersleeve

Abstract

Cancer vaccines significantly improve survival for some patients; although for unclear reasons, seemingly similar patients can receive little or no benefit. New biomarkers of cancer vaccine efficacy should improve understanding of in vivo vaccine function and help make vaccines more broadly effective. Serum anti-glycan antibodies are potential biomarkers for tracking response to cancer vaccines. Although tumors and many vaccines express antigenic carbohydrates, immune responses to these carbohydrates are relatively understudied. We used high-throughput glycoarrays to study anti-glycan humoral responses to the prostate cancer vaccine PROSTVAC (recombinant vaccinia and fowlpox genetically modified to express PSA and three co-stimulatory molecules). In two independent and blinded sample sets, humoral responses to the terminal disaccharide of Forssman xenoantigen (GalNAc-α1,3-GalNAc-β) correlated with survival of vaccinated subjects. Interestingly, survival did not correlate with humoral responses to Forssman disaccharide in controls, who received inactive viral vectors as placebo. Humoral responses to Forssman disaccharide were traced to PROSTVAC’s viral vectors, which likely acquired this glycan during propagation in non-human cells. These results provide the first evidence of enhanced vaccine efficacy associated with immune responses to glycans displayed on a cancer vaccine. Additionally, these findings suggest that change in anti-Forssman antibodies is a promising biomarker for response to PROSTVAC.

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