# Engineering bacteriophage Qβ conjugates with tumor associated carbohydrate antigens as multi-component anti-cancer vaccines

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2021 · $100,000

## Abstract

Project Summary
 Targeting tumor-associated carbohydrate antigens (TACAs) for anticancer vaccines is exceptionally
attractive because many TACAs are highly expressed on multiple types of cancer cells with no or negligible
expression on normal cells. While passive immunity utilizing anti-TACA monoclonal antibodies has achieved
clinical success, developing a TACA based immunogen to elicit effective anti-cancer immunity has been
extremely difficult due to the notoriously low immunogenicity of TACAs. To address this challenge, exciting
preliminary results have been obtained showing that TACA-based vaccines can significantly reduce cancer
induced death by delivering a prototypical TACA, the Tn antigen, using virus like particle bacteriophage Qβ.
 In this proposal, new ground in TACA based cancer vaccine design will continue to be broken by
engineering Qβ to generate powerful anti-cancer immune responses. Building on the exciting preliminary results,
in Aim 1, an important tumor associated glycopeptide antigen human MUC-1 bearing Tn glycan will be targeted.
Using Qβ as the carrier, super-high titers of IgG antibodies were elicited against MUC1-Tn, which significantly
reduced tumor growth in mice, even in transgenic mice tolerant to human MUC1. Besides Tn and tumor
associated MUC1 glycopeptides, other TACAs including GD2 and SSEA-3 will be investigated as vaccine targets
to reduce the risk of tumor escape from immune surveillance and to kill purported cancer stem cells, a possible
cause for resistance to traditional treatments such as chemotherapy. In addition, guided by the crystal structure
of Qβ, Qβ mutants will be developed to reduce undesirable anti-Qβ antibodies and further boost desired anti-
TACA responses. Cytotoxic T cells can also kill cancer cells. In Aim 2, Qβ will be engineered to deliver cytotoxic
T cell epitopes and built-in adjuvants in addition to generating anti-TACA IgG antibodies. The comprehensive
antibody and cytotoxic T cell immune responses induced by Qβ-TACA-cytotoxic T cell epitope conjugate should
provide superior protection to immunized host against tumor development. To lay the groundwork for future
translation, in Aim 3, the vaccine efficacy in treating canine cancer patients will be established. Canines can
naturally develop cancer, which are clinically relevant large animal models for human diseases due to their high
similarities to human cancer. This will be the first of its kind trial of such TACA based vaccine constructs in
canine patients.
 Overall impacts: This project will establish a Qβ vaccine platform vastly superior to currently available
carriers to deliver both TACAs and cytotoxic T cell epitopes, which will elicit long-lasting anti-TACA IgG
antibodies and cytotoxic T cells for cancer treatment. Deeper understanding of the connections between
structural features of Qβ-TACA conjugates and anti-tumor immunity will exert a sustained impact on cancer
vaccine design and is essential for successful TACA-based anti-...

## Key facts

- **NIH application ID:** 10086853
- **Project number:** 5R01CA225105-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Xuefei Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 5
- **Project period:** 2018-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086853

## Citation

> US National Institutes of Health, RePORTER application 10086853, Engineering bacteriophage Qβ conjugates with tumor associated carbohydrate antigens as multi-component anti-cancer vaccines (5R01CA225105-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10086853. Licensed CC0.

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