The Utility of Poly(.GAMMA.-glutamic acid) Nanoparticles as Antigen Delivery Carriers in Dendritic Cell-Based Cancer Immunotherapy

Abstract

Cytotoxic T-lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) act in the immune surveillance system as major effector cells to eliminate malignant cells. Immunization with TAA-loaded dendritic cells (DCs) has great potential for treating cancer, because DCs are potent antigen-presenting cells capable of inducing antigen-specific CTLs by the primary activation of naive T-lymphocytes. The establishment of a non-cytotoxic and efficient antigen delivery method is required to improve the efficacy of DC-based cancer immunotherapy. We developed biodegradable poly(γ-glutamic acid) nanoparticles (γ-PGA NPs) that can efficiently entrap various proteins as antigen delivery carriers. γ-PGA NPs efficiently delivered entrapped antigenic proteins into DCs without cytotoxicity and presented antigens to DCs via major histocompatibility complex class I and II molecules. Immunization with TAA-loaded DCs using γ-PGA NPs inhibited tumor growth by inducing TAA-specific CTLs. These findings indicate that γ-PGA NPs can function as useful antigen delivery carriers in DC-based cancer immunotherapy.