Antibody opsonization of tumor cell membranes using hapten-PEG-lipid conjugates

Abstract

Dendritic cell (DC) immunotherapy is a newly developed type of tumor immunotherapy. As a method for generating antigen-presenting DCs, the phagocytosis of whole tumor cells (WTCs) opsonized with antibodies by DCs (antibody-dependent cellular phagocytosis, ADCP) is especially efficient. To opsonize tumor cells, tumor-specific antibodies are usually required. Therefore conventional ADCP was limited to tumor types for which antigens have been identified and antigen-specific antibodies are available. Herein, we developed a general method to promote ADCP by DCs using an arbitrary antibody and evaluated its antitumor effects. To opsonize tumor cells with a tumor-nonspecific antibody, we modified tumor cell surfaces with PEG-lipid-hapten conjugates and a conjugated anti-hapten antibody. By co-culturing DCs with the antibody-opsonized tumor cells, the phagocytosis and DC maturation rates were enhanced by ~20% and ~10%, respectively, compared with co-cultured non-opsonized tumor cells. The administration of tumor antigen-loaded matured DCs to mice resulted in enhanced tumor rejection and long-term survival. The advantages of this method are that tumor-specific antibodies are not required and DCs can present uncharacterized antigens by phagocytosing WTCs and associated antigens. Therefore, this method might be applicable to various types of tumors for which specific antigens have not yet been identified.