Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy

Li, Mingjing; Wang, Zhaoyu; Yan, Bocheng; Yin, Xiaona; Yue, Zhao; Fan, Yuding; Meng, Meng; Liu, Yonghui; Zhao, Wei

doi:10.1039/c9md00254e

Cited by 13 publications

(10 citation statements)

References 35 publications

(34 reference statements)

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“…Li and co-workers [158], utilized a 20-mer MUC1 tandem repeat sequence with a Tn antigen in the PDT*RP region conjugated to the fibroblast stimulating lipopeptide 1 (FSL-1, Pam 2 -CGDPKHPKSF) that supports recognition through TLR2 and TLR6 with or without helper T cell epitopes. Immunological results indicate that the tricomponent glycosylated vaccine design stimulated humoral and cellular immune responses that were almost 1.5 times higher than the candidate without the T helper epitope and the antibodies generated from tricomponent vaccine mice bound MCF-7 cancer cells much more effectively.…”

Section: Self-adjuvating Multicomponent Vaccinesmentioning

confidence: 99%

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Beckwith

Čudić

2020

Seminars in Immunology

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The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. It has frequently been reported that MUC1, the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern, in human carcinomas of the epithelium. The presence of incomplete or truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play a key role in tumor initiation, progression, and metastasis. Accumulating evidence suggests that expression of TACAs is associated with tumor escape from immune defenses. In this report, we will give an overview of the oncogenic functions of MUC1 that are exerted through. TACA interactions with endogenous carbohydrate-binding proteins (lectins). These interactions often lead to creation of a protumor microenvironment, favoring tumor progression and metastasis, and tumor evasion. In addition, we will describe current efforts in the design of cancer vaccines with special emphasis on the synthetic MUC1 glycopeptide vaccines. Analysis of key factors that govern structure-based design of immunogenic MUC1 glycopeptide epitopes are described. The role of TACA type, position, and density on observed humoral and cellular immune responses is evaluated.

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Section: Self-adjuvating Multicomponent Vaccinesmentioning

confidence: 99%

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Beckwith

Čudić

2020

Seminars in Immunology

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“…Likewise, antibody-mediated CDC assay also indicated that the anti-1 sera could mediate strongest killing rate against HER2 overexpressing BT474 breast cancer cells than anti-sera stimulated by vaccine 2 and vaccine 3 under the same conditions, which supported the similar results in previous studies. 20,[23][24][25] Furthermore, tricomponent vaccine 1 with its simple lipopeptide adjuvant-helper T cell epitope P2-minimal epitope conjugated structure also exhibited Th1 and Th2-skewed responses, which strongly supported the self-adjuvanting vaccine strategy with multiple components. In addition, the in vivo results also indicated that immunoadjuvant Pam 3 CSK 4 could stimulated a stronger immune response than the helper T cell epitope.…”

Section: Discussionmentioning

confidence: 98%

“… 24 Zhao et al designed and synthesized a MUC1-based tricomponent vaccine by conjugating MUC1 antigen, a helper T cell epitope P2 (QYIKANSKFIGITE) with lipopeptide FSL-1, and the glycosylated tricomponent vaccine candidate enabled to induce the efficient elicitation of both humoral and cellular immune responses. 25 These studies provided strong evidence to support the design of multicomponent cancer vaccines.…”

Section: Introductionmentioning

confidence: 88%

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines

Feng

Wang

et al. 2021

RSC Adv.

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“…For example, in clinical application, a synthetic MUC1 peptide was used as a vaccine to strengthen the tumor-associated antigen presentation of dendritic cells and to activate cytotoxic T cells in resected and locally advanced pancreatic cancer [ 68 ]. Pancreatic cancer immunotherapy with MUC1-based vaccines reduced the tumor burden by inducing a cellular and humoral response [ 69 ]. The combination of MUC1 antibodies and radioisotopes is an interesting concept, but the side effects of radiotherapy such as neutropenia and thrombocytopenia as well as the high cost should be considered [ 70 , 71 ].…”

Section: Changes Of the Adaptive Metabolic Pathwaysmentioning

confidence: 99%

Pancreatic cancer and adaptive metabolism in a nutrient-deficient environment

Słotwiński¹,

Słotwińska²

2021

cejoi

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Despite tremendous progress in the treatment of many cancer types, leading to a significant increase in survival, pancreatic ductal adenocarcinoma (PDAC) is still burdened with high mortality rates (5-year survival rate < 9%) due to late diagnosis, aggressiveness, and a lack of more effective treatment methods. Early diagnosis and new therapeutic approaches based on the adaptive metabolism of the tumor in a nutrient-deficient environment are expected to improve the future treatment of PDAC patients. It was found that blocking selected metabolic pathways related to the local adaptive metabolic activity of pancreatic cancer cells, improving nutrient acquisition and metabolic crosstalk within the microenvironment to sustain proliferation, may inhibit cancer development, increase cancer cell death, and increase sensitivity to other forms of treatment (e.g., chemotherapy). The present review highlights selected metabolic signaling pathways and their regulators aimed at inhibiting the neoplastic process. Particular attention is paid to the adaptive metabolism of pancreatic cancer, including fatty acids, autophagy, macropinocytosis, and deregulated cell-surface glycoproteins, which promotes cancer cell development in an oxygen-deficient and nutrient-poor environment.

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Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy

Abstract: The designed tricomponent MUC1-based vaccine induced robust immune responses and exhibited a significant reduction in tumor burden.

Cited by 13 publications

References 35 publications

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines

Pancreatic cancer and adaptive metabolism in a nutrient-deficient environment

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