Optimization of Whole Tumor Cell Vaccines by Interaction with Phagocytic Receptors.

Abstract

The principal event in the function of whole-cell cancer vaccines is the ingestion of vaccine-delivered tumor antigen-containing material, which is performed by the patient’s antigen-presenting cells (APCs) through the employment of their phagocytic receptors. The goal of the present study was to identify the phagocytic receptors critical for the therapeutic efficacy of whole-cell cancer vaccines. The model of photodynamic therapy (PDT)-generated vaccines based on mouse SCCVII tumors was utilized, with in vitro expanded SCCVII cells treated by PDT serving as the vaccine material used for treating mice bearing established SCCVII tumors. The therapeutic impact, monitored as delayed progression of vaccinated tumors, was almost completely eliminated when antibodies specifically blocking the activity of LOX-1 scavenger receptor were administered to mice 30 min before vaccination. Similar, but much less pronounced, impacts were found with antibodies neutralizing the activity of CR3/CR4 receptors recognizing complement-opsonized vaccine cells, and with those blocking activating Fcγ receptors that recognized IgG antibody-based opsonins. A strikingly contrary action, a greatly enhanced tumor control by the vaccine, was found by blocking immune inhibitory receptor, FcγRIIB. The reported findings establish, therefore, an attractive strategy that can be effectively exploited for potent therapeutic enhancement of PDT-generated (and probably other) whole-cell tumor vaccines.