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

Thekke Veettil, K and Jayaraman, N (2024) Lymph Node Targeting Mediated by Albumin Hitchhiking of Synthetic Tn Glycolipid Leads to Robust In Vivo Antibody Production. In: Advanced Healthcare Materials .

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Abstract

Tn antigen is a tumor-associated carbohydrate antigen, which is present prominently on the tumor cell surfaces and attracts an interest in vaccine development. This work demonstrates that a synthetic Tn antigen carrying glycoconjugate forms a complex with circulating albumin, delivers the antigen to lymph nodes (LNs), and leads to the efficient production of antibodies 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 a rate 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 LNs, specifically leading to a robust humoral immune response. ELISA titers show superior binding, with a saturation dilution of 1:51 200 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 LNs, specifically at the subcapsular sinus and interfollicular areas. The work highlights the potential of albumin-mediated target delivery strategy for cancer immunotherapies. © 2024 Wiley-VCH GmbH.

Item Type:	Journal Article
Publication:	Advanced Healthcare Materials
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to John Wiley and Sons Inc.
Keywords:	Antibodies; Antigens; Carbohydrates; Cell membranes; Diseases; Mammals; Rate constants; Tumors, Albumin; Antibody production; Bovine serum albumins; Cancer; Glyco lipids; Glycoconjugates; Immunotherapy; In-vivo; Lymph node; Tumour cells, Vaccines
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	21 May 2024 09:08
Last Modified:	21 May 2024 09:08
URI:	https://eprints.iisc.ac.in/id/eprint/84895

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