The Biocomplex Assembled from Antigen Peptide and Toll-like Receptor Agonist Improved the Immunity against Pancreatic Adenocarcinoma In Vivo.

Abstract

One of the biggest challenges in cancer immunotherapy is generating robust cancer-specific immunity. This work describes using a biocomplex assembled from a toll-like receptor agonist CpG oligodeoxynucleotide 1826 (CpG) and a pancreatic cancer antigen peptide mesothelin for tuning pancreatic tumor immunity. This biocomplex was assembled via electrostatic interactions and characterized in size, morphology, zeta potential, and cargo loading. The effect of biocomplex on cell viability and activation of DCs and macrophages were measured by flow cytometry. The production of cytokines (GM-CSF, TNF, and IL-6) was evaluated by using ELISA kits. The effect of biocomplex on tumor cell proliferation was also evaluated by in vivo tumor model. We can modulate the surface charge of the biocomplex by simply varying the ratios of the two components. In cell models, this biocomplex did not impact cell viability in the antigen-presenting cell (i.e., dendritic cell and macrophage)-directed immunity. Moreover, this biocomplex regulated the secretion of tumor-related cytokines (i.e., GM-CSF, TNF, and IL-6) and promoted the activation of immune cell surface markers (i.e., CD80+, CD86+, and CD40+). In the mouse model, the biocomplex inhibited the tumor burden effectively and promoted the production of effector cytokines. The present studies showed that the biocomplex with antigen peptide and toll-like receptor agonist was able to potentiate the antitumor immunity in vivo. This study will help understanding of immunity in pancreatic cancer and developing new immune therapeutic strategies for pancreatic adenocarcinoma.