Synthetic poly(L-glutamic acid)-conjugated CpG exhibits antitumor efficacy with increased retention in tumor and draining lymph nodes after intratumoral injection in a mouse model of melanoma

摘要

There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8⁺ T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 h after injection, 26.5±16.9% of the injected PG-CpG dose versus 4.72±2.61% of free CpG remained at the tumor, and 1.53±1.22% of the injected PG-CpG versus 0.37±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.