Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells.

Previously, we have successfully targeted the mannose receptor (MR) expressed on monocyte-derived dendritic cells (DCs) using a fully human MR-specific antibody, B11, as a vehicle to deliver whole protein tumor antigens such as the human chorionic gonadotropin hormone (hCGbeta). Since MRs play a role in bridging innate immunity with adaptive immunity we have explored several toll-like receptor (TLR)-specific ligands that may synergize with MR targeting and be applicable as adjuvants in the clinic. We demonstrate that antigen-specific helper and cytolytic T cells from both healthy donors and cancer patients were effectively primed with B11-hCGbeta-treated autologous DCs when a combination of one or several TLR ligands is used.

Synergistic effects of combined therapy using paclitaxel and [90Y-DOTA]776.1 on growth of OVCAR-3 ovarian carcinoma xenografts.

Objective: 776.1 is a monoclonal antibody prepared against the human ovarian cancer antigen CA 125 that demonstrates preferential binding to the cell-associated form of the antigen and has shown promising results as an yttrium-90-labeled antibody in pre-clinical studies examining the effects on tumor growth in a murine xenograft model of human ovarian cancer. The purpose of the present study was to examine the effects of combined therapy with [90Y-DOTA]776.

Pharmacokinetics, biodistribution, and radioimmunotherapy with monoclonal antibody 776.1 in a murine model of human ovarian cancer.

776.1 is a murine IgG1 monoclonal antibody to the human ovarian cancer antigen CA 125 that has the unique property of having a clear preference for binding to the cell-associated form of the antigen. We have examined the tumor localization properties and efficacy of 776.

Early growth response transcription factors are required for development of CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage.

Progression of immature CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint to the CD4(+)CD8(+) stage requires activation of the pre-TCR complex; however, few of the DNA-binding proteins that serve as molecular effectors of those pre-TCR signals have been identified. We demonstrate in this study that members of the early growth response (Egr) family of transcription factors are critical effectors of the signals that promote this developmental transition. Specifically, the induction of three Egr family members (Egr1, 2, and 3) correlates with pre-TCR activation and development of CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint.