Dendritic Cell Vaccine(H. Lee Moffitt Cancer Center and Research Institute)

Dendritic cell vaccine (DCV) holds great potential in tumor immunotherapy owing to its potent ability in eliciting tumor‐specific immune responses. Aiming at engineering enhanced DCV, we report the first effort to construct a glycopolymer‐engineered DC vaccine (G‐DCV) via metabolicglycoengineering and copper‐free click‐chemistry. Model G‐DCV was prepared by firstly delivering tumor antigens, ovalbumin (OVA) into dendritic cells (DC) with fluoroalkane‐grafted polyethyleneimines, followed by conjugating glycopolymers with a terminal group of dibenzocyclooctyne (DBCO) onto dendritic cells. Compared to unmodified DCV, our G‐DCV could induce stronger T cell activation due to the enhanced adhesion between DCs and T cells. Notably, such G‐DCV could more effectively inhibit the growth of the mouse B16‐OVA (expressing OVA antigen) tumor model after adoptive transfer. Moreover, by combination with an immune checkpoint inhibitor, G‐DCV showed further increased anti‐tumor effects in treating different tumor models. Thus, our work provides a novel strategy to enhance the therapeutic effectiveness of DC vaccines.

Because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 (sPD-1) could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines. Very low levels of sPD-1 may indicate lack of an existing anti-cancer immune response; very high levels may indicate an active immune response that is suppressed. In between these extremes, a decrease in PD-1 following injections of an anti-cancer vaccine may indicate an enhanced immune response that has not been suppressed. Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients treated with a tumor cell vaccine (TCV) and 17 treated with a dendritic cell vaccine (DCV). Survival was better in DCV-treated patients. sPD-1 was measured at week-0, one week before the first of three weekly subcutaneous injections, and at week-4, one week after the third injection. The combination of a very low baseline sPD-1, or absence of a very high PD-1 at baseline followed by a decline in sPD-1 at week-4, was predictive of surviving three or more years in DCV-treated patients, but not TCV-treated. Among DCV-treated patients, these sPD-1 criteria appropriately classified 8/10 (80%) of 3-year survivors, and 6/7 (86%) of patients who did not survive three years. These preliminary observations suggest that sPD-1 might be a useful biomarker for melanoma patients being considered for treatment with this DCV vaccine, and/or to predict efficacy after only three injections, but this would have to be confirmed in larger studies.