A novel cancer immunotherapy based on the combination of a synthetic carbohydrate-pulsed dendritic cell vaccine and glycoengineered cancer cells

Oncotarget
Lei QiuJunping Zhang

Abstract

Immune tolerance to tumor-associated carbohydrate antigens (TACAs) has severely restricted the usefulness of most TACAs. To overcome this problem, we selected a sialylated trisaccharide TACA, GM3, as a target antigen, and tested a new immunotherapeutic strategy by combining metabolic bioengineering with dendritic cell (DC) vaccination. We engineered cancer cells to express an artificial structure, N-phenylacetyl-D-neuraminic acid, in place of the natural N-acetyl-D-neuraminic acid of GM3 by using N-phenylacetyl-D-mannosamine (ManNPhAc) as a biosynthetic precursor. Next, we selectively targeted the bioengineered cancer cells by vaccination with DCs pulsed with the GM3 N-phenylacetyl derivative. Vaccination with GM3NPhAc-KLH-loaded DCs elicited robust GM3NPhAc-specific T cell-dependent immunity. The results showed that this strategy could significantly inhibit FBL3 tumor growth and prolong the survival of tumor-bearing mice; B16F10 lung metastases could also be reduced. These findings lay out a new strategy for overcoming immune tolerance to TACAs, such as GM3, for the development of effective tumor immunotherapies.

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Citations

Jul 21, 2016·Angewandte Chemie·Paul R WratilWerner Reutter
Mar 24, 2017·BioMed Research International·Grzegorz DyduchKrzysztof Okoń
Nov 30, 2019·Nature Reviews. Chemistry·Christian AgatemorKevin J Yarema
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Mar 8, 2018·Medicinal Research Reviews·Meng-Man WeiXin-Shan Ye
Dec 19, 2017·International Immunopharmacology·Xiangwei YuanXianlong Zhang

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Datasets Mentioned

BETA
GM3

Methods Mentioned

BETA
flow cytometry
ELISA
Assay
enzyme-linked immunosorbent spot

Software Mentioned

GraphPad Prism

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