Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth

• Published in: Vaccine Vol. 35; no. 43; pp. 5842 - 5849
• Main Authors: Bryson, Paul D., Han, Xiaolu, Truong, Norman, Wang, Pin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 13.10.2017; Elsevier Limited
• Subjects: Alpha-lactalbumin; Animals; Antigen Presentation - immunology; Antigens; Antigens, Neoplasm - immunology; Antitumor activity; Autoantigens - immunology; Breast cancer; Breast cancer immunotherapy; Cancer vaccine; Cancer vaccines; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; Clinical trials; Cloning; Dendritic cells; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; Drug delivery systems; ERBB2/Her2; Female; Genes; Genetic Vectors - immunology; Immune response; Immunotherapy; Immunotherapy - methods; Kinases; Laboratory animals; Lentiviral vector; Lentivirus - immunology; Mammary gland; Mammary Neoplasms, Animal - immunology; Mice; Mice, Inbred BALB C; Mutagenesis; Plasmids; Proteins; Receptor, ErbB-2 - immunology; Rodents; Tumors; Vaccines; SFC; Cancer vaccine; Lentiviral vector; Breast cancer immunotherapy; COPA; MOI; Alpha-lactalbumin; LV; ERBB2/Her2
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.09.017

[Display omitted] •A dendritic cell-targeted lentivector vaccine delivers breast cancer antigens.•Immunization with the ERBB2 antigen generates a strong CD8T cell response.•A single immunization protects against mammary tumors in a self-antigen environment. Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors asa breast cancer vaccine could lead to an improved immune response against self-antigens found in breast cancer tumors. Indeed, single injections of the vaccine vectors were able to amplify antigen-specific CD8T cells 4–6-fold over naïve mice, similar to the best published vaccine regimens. Immunization of these mice completely inhibited tumor growth in a foreign antigen environment (LV-ERBB2 in wildtype mice), and it reduced the rate of tumor growth in a self-antigen environment (LV-Lalba in wildtype or LV-ERBB2 in MMTV-huHER2 transgenic). These results show that a single injection with targeted lentiviral vectors can be an effective immunotherapy for breast cancer. Furthermore, they could be combined with other immunotherapeutic regimens to improve outcomes for patients with breast cancer.