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Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation

ABSTRACT: O-glycan analysis of the four MUC7 samples was performed by mass spectrometry.

INSTRUMENT(S): 6520A Quadrupole Time-of-Flight LC/MS

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Tina Iverson

PROVIDER: MSV000088327 | MassIVE | Sun Nov 07 10:33:00 GMT 2021

REPOSITORIES: MassIVE

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Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, 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. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his anti-glycan humoral responses occuring in the first months after treatment with PROSTVAC-VF. Results: Humoral responses to the terminal Forssman disaccharide (Fsdi) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with four-fold or larger anti-Fsdi responses relative to subjects with little or no anti-Fsdi response. 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-Fsdi humoral responses were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new biomarker for monitoring benefical responses to PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination and post-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgM levels for the validation set measured at serum dilution of 1:50 are detailed here. The screen for response biomarkers identified anti-glycan humoral responses that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Raw data on SuperSeries GSE50410 record.

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Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation

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