Lymph Node Targeting Mediated by Albumin Hitchhiking of Synthetic Tn Glycolipid Leads to Robust In Vivo Antibody Production.

Abstract

Tn antigen is a tumor-associated carbohydrate antigen (TACA), which is present prominently on the tumor cell surfaces and attracts an interest in the vaccine development. In this work, we demonstrate that a synthetic Tn antigen carrying glycoconjugate forms complex with circulating albumin, delivers the antigen to lymph nodes and leads to efficient production of antibody against the antigen. Synthetic Tn antigen glycoconjugate, possessing DSPE-PEG2000 linker and lipophilic moieties, undergoes micellization in PBS buffer. In the presence of bovine serum albumin (BSA), demicellization of the glycolipid occurs, with rate a constant of 0.18 min-1. In vitro studies show that the glycoconjugate binds preferentially to BSA in the presence of cells. Immunological assessments in mice models reveal the albumin-enabled delivery of the Tn glycoconjugate to antigen presenting cells in the lymph nodes specifically, leading to a robust humoral immune response. ELISA titres show superior binding, with a saturation dilution of 1:51200 for Tn glycoconjugate, in comparison to that mediated by the Tn-BSA covalent conjugate with a saturation dilution of 1:6400. Immunohistochemical staining shows delivery of Tn glycoconjugate at the lymph nodes, specifically at the subcapsular sinus and interfollicular areas. The work highlights the potential of albumin-mediated target delivery strategy for cancer immunotherapies. This article is protected by copyright. All rights reserved.