Enhanced immunotherapeutic effect of B cell based vaccine transduced with modified adenoviral vector

Abstract

For successful clinical outcome of tumor immunotherapy, proper generation of strong immune responses against tumor antigen is required. Cell based vaccine is one of the strategy to induce appropriate immune responses. In previous studies we established NKT ligand loaded, adeoviral antigen transduced-B cell based anticancer cellular vaccine that efficiently induced a wide spectrum of immune responses against tumor antigen. However the lack of the coxsakivirus-adenovirus receptor(CAR) on B cells limits the adenoviral Ag gene delivery. In this study, we established a modified adenoviral vector(Ad-k35) whose fiber structure was substituted with adenovirus serotype 35, encoding truncated breast cancer antigen Her2/neu(Ad-k35HM), to enhance tumor antigen gene delivery to B cells. Using Ad-k35HM, we observed increased expression of tumor antigen on both human and mouse B cells. And Ad-k35HM transduced B cell vaccine elicited antigen specific strong cellular and humoral immune responses and these responses was further enhanced with additional loading of derivative of NKT ligand KBC009. Ad-k35HM transduced, KBC009 loaded B cell vaccination efficiently suppressed in vivo established tumor growth in a mice model. These findings showed modified adenoviral vector Ad-k35 could be appropriate for the preclinical and clinical development of B cell based anticancer immunotherapy.