Abstract 2888: Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 2888
• Main Authors: Bryson, Paul D., Han, Xiaolu, Truong, Norman, Wang, Pin
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-2888

Abstract Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. In contrast, active immunotherapy through therapeutic vaccination has yet to be proven clinically effective for breast cancer. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To achieve this in vivo, we have pseudotyped lentiviral vector vaccines with a modified Sindbis Virus glycoprotein that targets the C-type lectin DC-SIGN, which is expressed on DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors as a breast cancer vaccine could lead to an improved immune response against self antigens found in breast cancer tumors. Such an improved immune response may help to prevent or slow tumor growth in breast cancer models. To test these hypotheses, we have constructed lentiviral vectors encoding each of the breast cancer antigens, human Her2 (ERBB2) and mouse alpha-lactalbumin (Lalba). Single injections were able to amplify antigen-specific CD8 T cells to 1.6% of total CD8 T cells in BALB/cJ mice and 0.7% in transgenic ERBB2 mice. This compares favorably with recently published vector vaccines, which have elicited 0.9% and <0.1% antigen-specific CD8 T cells under similar conditions. In addition, DC-targeted immunization of these mice completely inhibited tumor growth in a foreign antigen environment (ERBB2 + wt BALB/cJ), while it significantly reduced the rate of tumor growth in a self-antigen environment (Lalba + BALB/cJ or ERBB2 + FVB/Tg.MMTV.f.huHER2 #5). Our data show that these vectors alone can provide an effective therapy. Future studies may be able to improve these responses by combining DC-targeted immunization with established methods of reducing cancer immunosuppression. Thus, lentivector vaccines may be an excellent component to future clinical vaccine trials, either by themselves or in combination with other chemo- and immunotherapies. Citation Format: Paul D. Bryson, Xiaolu Han, Norman Truong, Pin Wang. Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2888. doi:10.1158/1538-7445.AM2014-2888