Breast cancer is the second most common type of cancer in females, causing over 40,000 deaths in the United States annually. Recently, cancer vaccines have arisen as a potential therapy and several target antigens have been identified in Breast cancer, including Her2/neu antigen. The goal of cancer vaccines is to generate effector T cells that are able to infiltrate and kill the tumor cells. We propose to generate a single recombinant Listeria monocytogenes capable of targeting cancer cells and tumor vasculature by concomitant expression of Her2 and HMW-MAA, which is expressed in pericytes and plays a role in tumor angiogenesis. To address this challenge, a dual-expression Lm platform is created by expressing Her2 from the chromosome and HMW-MAA from a plasmid. To enhance immunogenicity, both antigens are fused to the virulence factor listeriolysin-O and immune responses and therapeutic efficacy of the dual-expression system will be evaluated, including analysis of tumor-infiltrating lymphocytes and tumor vasculature. Delivery of an anti-angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect in impacting tumor growth by targeting blood vessels, which might enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy, besides creating a flexible platform for future use.
Public Health Relevance: Breast cancer is a major health problem in female population, causing the death of over 40,000 American men annually. In this SBIR Phase I project, Advaxis Inc. will construct a novel, clinically suitable recombinant Listeria monocytogenes capable of targeting Her2 expressing breast cancer cells and tumor vasculature concomitantly, which will be tested in a mouse tumor model.
Public Health Relevance Statement: Narrative Breast cancer is a major health problem in female population, causing the death of over 40,000 American men annually. In this SBIR Phase I project, Advaxis Inc. will construct a novel, clinically suitable recombinant Listeria monocytogenes capable of targeting Her2 expressingBreast cancer cells and tumor vasculature concomitantly, which will be tested in a mouse tumor model.
NIH Spending Category: Biotechnology; Breast Cancer; Cancer; Immunization; Prevention; Vaccine Related
Project Terms: ATGN; Address; Adherence; Adherence (attribute); Adhesion Molecule; Adventitial Cell; Affect; American; American Indian and Alaska Native; Angiogenesis Antagonists; Angiogenesis Blockers; Angiogenesis Inhibitors; Angiogenetic Antagonists; Angiogenic Antagonists; Angiostatic Agents; Animals; Anti-Angiogenetic Agents; Anti-Angiogenic Agents; Anti-Angiogenic Drugs; Antiangiogenesis Agents; Antiangiogenic Agents; Antigen Targeting; Antigens; Antineoplastic Vaccine; Asians; Attenuated; Attenuated Live Virus Vaccine; Blood Vessels; Breast Cancer Cell; CD4 Positive T Lymphocytes; CD4 T cells; CD4 lymphocyte; CD4+ T cell; CD4+ T-Lymphocyte; CD4-Positive Lymphocytes; CD8; CD8 Cell; CD8 lymphocyte; CD8+ T-Lymphocyte; CD8-Positive Lymphocytes; CD8-Positive T-Lymphocytes; CD8B; CD8B1; CD8B1 gene; Cancer Cause; Cancer Etiology; Cancer Patient; Cancer Prognosis; Cancer Treatment; Cancer Vaccines; Cancer of Breast; Cancer of Cervix; Cancer of the Ovary; Cancer of the Uterine Cervix; Cancers; Cause of Death; Cell Adhesion Molecules; Cell surface; Cells; Cells, CD4; Cervical Cancer; Cervix Cancer; Cessation of life; Chemotherapy-Hormones/Steroids; Chimera Protein; Chimeric Proteins; Chromosomes; Complex; Death; Development; Diagnosis; Disease; Disorder; Endocrine Gland Secretion; Endocrine Therapy; Endothelial Cells; Female; Fusion Protein; Future; Gastrointestinal Tract, Pancreas; Genomics; Goals; Health; Hispanic Populations; Hispanics; Hispanics or Latinos; Hormonal Therapy; Hormones; Human; Human Breast Cancer Cell; Human, General; ITX; Immune; Immune response; Immunization; Immunofluorescence; Immunofluorescence Immunologic; Immunologic Stimulation; Immunologic, Immunofluorescence; Immunological Stimulation; Immunologically Directed Therapy; Immunostimulation; Immunotherapeutic agent; Immunotherapy; Infiltration; Inhibitors, Angiogenetic; Inhibitors, Angiogenic; Invaded; Killings; L. monocytogenes; LYT3; Latino Population; Lead; Life; Listeria; Listeria monocytogenes; Listeria monocytogenes hlyA protein; Listeriolysin; Live-attenuated Vaccine; Lymphocyte; Lymphocytic; Malignant Cell; Malignant Cervical Neoplasm; Malignant Cervical Tumor; Malignant Neoplasm Therapy; Malignant Neoplasm Treatment; Malignant Neoplasm of the Cervix; Malignant Neoplasms; Malignant Ovarian Neoplasm; Malignant Ovarian Tumor; Malignant Tumor; Malignant Tumor of the Breast; Malignant Tumor of the Cervix; Malignant Tumor of the Cervix Uteri; Malignant Tumor of the Ovary; Malignant Uterine Cervix Neoplasm; Malignant Uterine Cervix Tumor; Malignant neoplasm of breast; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Mammals, Mice; Man (Taxonomy); Man, Modern; Mice; Modeling; Molecular; Murine; Mus; Neovascularization Inhibitors; Pacific Island Americans; Pacific Islander; Pacific Islander American; Pancreas; Pancreatic; Pathogenicity Factors; Patients; Pb element; Pericapillary Cell; Pericytes; Perivascular Cell; Phase; Plasmids; Play; Population; Pre-Clinical Model; Preclinical Models; Protein Fragment; Proteins; Recombinants; Resistance; Role; Rouget Cells; SBIR; SBIRS (R43/44); Sensitization, Immunologic; Sensitization, Immunological; Site; Skin Cancer, Non-Melanoma; Skin Carcinoma; Small Business Innovation Research; Small Business Innovation Research Grant; Solid Neoplasm; Solid Tumor; Spanish Origin; Staging; Stomach; System; System, LOINC Axis 4; T-Cells; T-Lymphocyte; T4 Cells; T4 Lymphocytes; T8 Cells; T8 Lymphocytes; Technology; Testing; Therapeutic; Therapeutic Agents; Therapeutic Hormone; Thymus-Dependent Lymphocytes; Treatment Efficacy; Tumor Angiogenesis; Tumor Antigens; Tumor Cell; Tumor Tissue; Tumor-Associated Antigen; Tumor-Infiltrating Lymphocytes; United States; Up-Regulation; Up-Regulation (Physiology); Upregulation; Vaccination; Vaccines; Vaccines, Neoplasm; Vaccines, Tumor; Virulence Factors; Woman; antiangiogenic; anticancer therapy; bacteria vector; bacterial vector; base; cancer cell; cancer therapy; cancer type; cell adhesion protein; cell mediated immune response; density; disease/disorder; expression vector; flexibility; gastric; gene product; heavy metal Pb; heavy metal lead; helper T cell; hispanic community; hlyA protein, Listeria monocytogenes; hormone therapy; host response; immune therapy; immunogen; immunogenicity; immunologic preparation; immunoresponse; immunotherapeutics; improved; in vivo; interest; lisA protein, Listeria monocytogenes; listeriolysin O; lymph cell; malignancy; malignant breast neoplasm; man; man's; melanoma-associated antigen; men; men's; neoplasm/cancer; neoplastic cell; neovascularization; nonmelanoma skin cancer; novel; oriental; ovarian cancer; patient population; protein expression; public health relevance; resistant; response; social role; success; therapeutic efficacy; therapeutically effective; thymus derived lymphocyte; tumor; tumor growth; tumor-specific antigen; vascular; vascular inflammation; vector
