Ex vivo activation of dendritic cells via coacervate-mediated exogenous tumor cell lysate delivery

For the successful development of various cellular products in cancer immunotherapy, an effective ex vivo priming technique for immune cells is often required. Among a variety of immunomodulatory substances, tumor cell lysates (TCLs) have been considered a robust immune activator with high adjuvanticity and tumor antigen population. Therefore, the present study suggests a novel ex vivo dendritic cell (DC) priming technique that utilizes (1) squaric acid (SqA)-mediated oxidation of source tumor cells to obtain antigenic TCLs with an increased immunogenic potential and (2) a coacervate (Coa) colloidal complex as an exogenous TCL carrier. Elevated oxidation by SqA-treated source tumor cells resulted in an increased immunogenic potential, indicated by a high level of damage-associated molecular pattern molecules in TCLs that could sufficiently stimulate DCs. Moreover, to effectively deliver these exogenous immunomodulating TCL DCs, Coa (i.e., a colloidal micro-carrier using cationic mPEGylated poly(ethylene arginyl aspartate diglyceride) and anionic heparin) was utilized for the sustained release of cargo TCLs and for preserving their bioactivity. Coa-mediated ex vivo delivery of SqA-treated TCLs (SqA-TCL-Coa) effectively promoted DC maturation through the enhanced uptake of antigens into target DCs, increased expression of DC activation markers, facilitated secretion of pro-inflammatory cytokines from activated DCs, and improved major histocompatibility complex-I dependent cross-presentation of a colorectal cancer specific antigen. Therefore, based on antigenic and adjuvant behaviors, our Coa-mediated exogenous delivery of SqA-TCL could be a promising application as a facile ex vivo DC priming strategy for further cell-based cancer immunotherapies.