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 Q? 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 Q? 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 Q?-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 Q?-tumor antigen conjugate to reduce metastasis will be established. With its ability to induce potent immunity, the Q? construct can protect the immunized host from breast cancer development and recurrence. OVERALL IMPACT. A new Q? 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.
Public Health Relevance Statement: Project narrative Cancer is a leading cause of death in the world. The availability of effective anti-cancer vaccines will be a quantum leap for cancer treatment and prevention. In this SBIR phase I project, a unique platform based on bacteriophage Q? will be developed to deliver cancer antigens, protect the immunized host from breast cancer development, and lay the ground work for human clinical trials.
Project Terms: Active Immunization; anti-cancer; Antibodies; Antibody Response; Antigen Targeting; Antigens; B-Lymphocyte Epitopes; Bacteriophages; base; Biotechnology; Breast; Breast cancer metastasis; Breast Cancer Model; Breast Cancer Patient; breast cancer vaccine; cancer cell; Cancer Etiology; Cancer Patient; cancer prevention; cancer recurrence; cancer therapy; Cancer Vaccine Related Development; Cancer Vaccines; Carbohydrates; Cause of Death; Cellular Immunity; Chemosensitization; Chemotherapy and/or radiation; chimeric antigen receptor T cells; Clinical; Clinical Research; Clinical Trials; clinically relevant; Colon Carcinoma; combat; Crystallization; Data; Development; Disease-Free Survival; Encapsulated; Engineering; Epitopes; fighting; Generations; Glycopeptides; Goals; Gold; head-to-head comparison; Human; Humoral Immunities; Immune; immune checkpoint; Immune response; Immunity; Immunization; Immunize; immunogenic; immunogenicity; Immunoglobulin G; Immunotherapy; innovation; Keyhole Limpet Hemocyanin; Lead; Legal patent; Licensing; Long-Term Effects; malignant breast neoplasm; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant Neoplasms; Mediation; Memory; Metastatic Neoplasm to the Lung; Methodology; Michigan; Mission; Modeling; Monoclonal Antibodies; mortality; mouse model; Mucin 1 protein; Mus; mutant; National Cancer Institute; neoantigens; Neoplasm Metastasis; neoplastic cell; Normal Cell; novel; novel vaccines; Operative Surgical Procedures; outcome forecast; Patients; Phase; Polysaccharides; preclinical study; prevent; Prevention therapy; Process; Production; Protein Engineering; quantum; Recurrence; Resolution; response; side effect; Small Business Innovation Research Grant; standard of care; Structure; success; Surface; System; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Therapeutic; three dimensional structure; Transgenic Mice; triple-negative invasive breast carcinoma; tumor; Tumor Antigens; Tumor Immunity; Universities; Vaccines; Work
