A novel human-derived antibody against NY-ESO-1 improves the efficacy of chemotherapy

We investigated whether antibodies against intracellular tumor-associated antigens support tumor-specific immunity when administered together with a treatment that destroys the tumor. We propose that released antigens form immune complexeswith the antibodies, which are then efficiently taken up by dendritic cells. We cloned the first human monoclonal antibodies against the Cancer/Testis (CT) antigen, NY-ESO-1. We tested whether the monoclonal anti- NY-ESO-1antibody (12D7) facilitates cross-presentationof a NY-ESO-1-derived epitope by dendritic cellsto human CD8+ T cells, and whether this results in the maturation of dendritic cellsin vitro . We investigated the efficacy of 12D7 in combination with chemotherapy using BALB/c mice bearing syngeneic CT26 tumors that express intracellular NY-ESO-1. Human dendritic cellsthat were incubated with NY-ESO-1:12D7 immune complexesefficiently stimulated NY-ESO-1157–165 /HLA-A2-specific human CD8+ T cells to produce interferon-γ, whereas NY-ESO-1alone did not. Furthermore, the incubation of dendritic cellswith NY-ESO-1:12D7 immune complexesresulted in the maturation of dendritic cells. Treatment of BALB/c mice that bear CT26/ NY-ESO-1tumors with 5-fluorouracil (5-FU) plus 12D7 was significantly more effective than chemotherapy alone. We propose systemic injection of monoclonal antibodies (mAbs) against tumor-associated antigens plus a treatment that promotes the local release of those antigens resulting in immune complexformation as a novel therapeutic modality for cancer. This article was published in Cancer Immunity , a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer ImmunologyResearch .