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

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...

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Detalles Bibliográficos
Autores principales: Qiu, Lei, Li, Jie, Yu, Shichong, Wang, Qianli, Li, Yinghua, Hu, Zhenlin, Wu, Qiuye, Guo, Zhongwu, Zhang, Junping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467142/
https://www.ncbi.nlm.nih.gov/pubmed/25760071
Descripción
Sumario: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.