A Novel Vaccine Strategy to Target Breast Cancer Enabled by Proprietary Mutant Bacteriophage Qbeta-Tumor Antigen Conjugates

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Project summary: Anti-cancer vaccines can be a highly attractive approach for tumor protection and treatment due to the potential for providing long term immunity with few side effects. However, it has been highly challenging to develop successful anti-cancer vaccines. Due to the low inherent immunogenicity of tumor antigens, it is critical that immunogenic carriers are available to powerfully boost the immune responses to tumor antigens. Iaso Therapeutics is a startup company spun out of Michigan State University. The mission of Iaso is to develop next generation vaccines by targeting an important class of tumor antigens, i.e., tumor associated carbohydrate and glyco-conjugate antigens. In this application, Iaso aims to develop a unique proprietary carrier system based on bacteriophage Qβ to deliver cancer antigens, as represented by the tumor associated mucin- 1 (tMUC1), and to generate superior immunity to combat breast cancer. Mucin-1 protein is a highly attractive target for anti-cancer vaccine development, as tumor associated tMUC1 glycopeptides are considered neoantigens due to their different glycan structures compared to the counterpart on normal cells. Furthermore, tMUC1 is expressed at high levels on many types of tumor cells, such as breast, pancreatic, colon and lung cancers. Clinical studies have shown that patients including breast cancer patients with high levels of anti-tMUC1 antibodies have significantly better prognosis and disease-free survival. However, it has been highly challenging to develop effective tMUC1 based anti-cancer vaccines to induce sufficient levels of anti-tMUC1 immunity to be protective. In aim 1 of this Phase I project, based on the discovery of key protective epitope of tMUC1, we will engineer bacteriophage Qβ to deliver tMUC1 and elicit superior IgG antibody responses. Furthermore, new methodologies will be developed to activate T cells specific against breast cancer antigens, thus engaging both humoral and cellular immunity to fight breast cancer. In aim 2, the efficacy of the lead Qβ-tumor antigen conjugate will be evaluated in a spontaneous mouse breast cancer model resembling triple negative breast cancer in human patients. Furthermore, as cancer metastasis is a major cause of cancer mortality, mouse models of breast cancer metastasis will be developed and the capability of the lead Qβ-tumor antigen conjugate to reduce metastasis will be established. With its ability to induce potent immunity, the Qβ construct can protect the immunized host from breast cancer development and recurrence. OVERALL IMPACT. A new Qβ vaccine platform vastly superior to currently available carriers is developed to deliver tumor antigens, eliciting high levels of antibody and T cell immune responses to reduce invasive breast cancer occurrence and metastasis.