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.
References
Jan 1, 1987·Journal of the National Cancer Institute·T TsuchidaR F Irie
Jul 1, 1996·CA: a Cancer Journal for Clinicians·D L Morton, A Barth
Nov 1, 1996·Cancer Immunology, Immunotherapy : CII·G Ragupathi
May 20, 1998·Seminars in Surgical Oncology·D W OllilaD L Morton
Jun 3, 2000·Annual Review of Immunology·L Fong, E G Engleman
Apr 5, 2001·Glycobiology·O T KepplerW Reutter
Aug 18, 2001·Cell·A Lanzavecchia, F Sallusto
Aug 18, 2001·Cell·J BanchereauG Schuler
Dec 3, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Susan F SlovinHoward I Scher
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lee M KrugPhilip O Livingston
Dec 21, 2004·Expert Review of Vaccines·Leona A Holmberg, Brenda M Sandmaier
Feb 4, 2005·Journal of Medicinal Chemistry·Yanbin PanZhongwu Guo
Jun 3, 2005·Nature Reviews. Drug Discovery·Danielle H Dube, Carolyn R Bertozzi
Mar 15, 2006·Biochemistry·Peter ChefaloClifford V Harding
Mar 31, 2006·Glycobiology·Mariko NoguchiJin-ichi Inokuchi
Nov 16, 2006·Bioconjugate Chemistry·Jian Wu, Zhongwu Guo
Sep 26, 2007·Bioorganic & Medicinal Chemistry·Qianli WangZhongwu Guo
Sep 26, 2008·Bioconjugate Chemistry·Qianli WangZhongwu Guo
Feb 4, 2011·Journal of Biosciences·Min LiXinyu Qin
Sep 20, 2011·MedChemComm·Shichong YuZhongwu Guo
Apr 28, 2012·Cancer Immunology, Immunotherapy : CII·Lei QiuZhongwu Guo
May 17, 2013·Recent Patents on Endocrine, Metabolic & Immune Drug Discovery·André A R AleixoEddie F C Murta
Citations
Jan 19, 2017·Oncotarget·Heleen H Van AckerEva Lion
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
Dec 13, 2017·Oncotarget·Laura F HutchinsThomas Kieber-Emmons
Nov 18, 2015·Chembiochem : a European Journal of Chemical Biology·Bo ChengXing Chen
Mar 8, 2018·Medicinal Research Reviews·Meng-Man WeiXin-Shan Ye
Jul 22, 2018·Technology in Cancer Research & Treatment·Haiyan ZhangXiuli Wang
Dec 19, 2017·International Immunopharmacology·Xiangwei YuanXianlong Zhang
Oct 7, 2017·ACS Omega·Maqbool A SiddiquiJoseph J Barchi