# Novel approaches to study immune responses to post translational modifications for cancer detection

> **NIH NIH U01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $448,752

## Abstract

Project Summary/Abstract
Despite advances in screening and treatment, mortalities from breast and lung cancers have remained high in
the US over the last 20 years. It is widely accepted that early detection is critical to improving outcomes in both
diseases. Both also rely on imaging for screening, but false positive and false negative detection are
associated with unnecessary biopsies, missed diagnoses, and costs. There is an urgent need for biochemical
markers that improve the performance of imaging technologies. Our laboratories have been successful at
identifying useful cancer biomarkers by exploiting patients’ own ability to produce antibodies against tumor-
associated antigens (TAA), referred to as tumor-associated autoantibodies (TAAb). With prior EDRN support,
we developed high-throughput programmable protein display methods for the rapid detection and validation of
autoantibody biomarker signatures in breast and lung cancers. Our breast cancer TAAb biomarkers have been
licensed and integrated into Videssa™ Breast that is now available as CLIA-certified test. Our triple negative
breast cancer markers have been validated in blinded phase 2 multicenter validation studies. These
demonstrate the great utility of TAAb in cancer early detection. However, the sensitivities of most TAAbs is
moderate and there is a suggestion that greater sensitivity and specificity could be obtained by examining
TAAb directed at aberrantly modified proteins in cancers. Our central hypothesis is that aberrant protein
glycosylation, a hallmark of breast and lung cancers, induces glycoprotein-specific TAAb that can be measured
as specific serum biomarkers of these cancers. Alterations in glycosylation are highly immunogenic, and there
is strong historical evidence for significant antibody responses to cancer-altered glycoproteins. However, all
current protein (or polypeptide) display tools allow limited or no post-translational modification. This historical
roadblock has prevented the identification of these biomarkers because of the lack of screening methods that
test immunogenic structural glycoproteins. We introduce a tool for the high-throughput display of full-length
proteins decorated with cancer-specific O-glycan structures. This will revolutionize the opportunity to screen
glycan-protein epitopes in their natural context. Our team comprises strong expertise in functional proteomics,
biomarker development, glycoproteomics, medical oncology and biostatistics. Targeted proteins will include:
the extra-cellular domains of relevant single pass membrane proteins, proteins known to be O-glycosylated
and overexpressed in the two cancers, and all known mucins. They will be translated in situ using human
ribosomes and chaperone proteins and then systematically decorated with Tn and STn O-GalNAc-type glycans
by consecutive addition of recombinant glycosyltransferases and sugar nucleotides to mirror what occurs in the
two cancers. Adhering to the principles of PRoBE des...

## Key facts

- **NIH application ID:** 9999320
- **Project number:** 5U01CA214201-05
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Karen Sue Anderson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,752
- **Award type:** 5
- **Project period:** 2016-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999320

## Citation

> US National Institutes of Health, RePORTER application 9999320, Novel approaches to study immune responses to post translational modifications for cancer detection (5U01CA214201-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999320. Licensed CC0.

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