PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy.

Abstract

Despite the promise and advantages of autologous cancer cell vaccination, it remains challenging to induce potent anti-tumor immune responses with traditional immunization strategies with whole tumor cell lysate. In this study, we sought to develop a simple and effective approach for therapeutic vaccination with autologous whole tumor cell lysate. Endogenous cell membranes harvested from cancer cells were formed into PEGylated nano-vesicles (PEG-NPs). PEG-NPs exhibited good serum stability in vitro and draining efficiency to local lymph nodes upon subcutaneous administration in vivo. Vaccination with PEG-NPs synthesized from murine melanoma cells elicited 3.7-fold greater antigen-specific cytotoxic CD8⁺ T lymphocyte responses, compared with standard vaccination with freeze-thawed lysate in tumor-bearing mice. Importantly, in combination with anti-programmed death-1 (αPD-1) IgG immunotherapy, PEG-NP vaccination induced 4.2-fold higher frequency of antigen-specific T cell responses (P < 0.0001) and mediated complete tumor regression in 63% of tumor-bearing animals (P < 0.01), compared with FT lysate + αPD-1 treatment that exhibited only 13% response rate. In addition, PEG-NPs + αPD-1 IgG combination immunotherapy protected all survivors against a subsequent tumor cell re-challenge. These results demonstrate a general strategy for eliciting anti-tumor immunity using endogenous cancer cell membranes formulated into stable vaccine nanoparticles.