A therapeutic HPV16 E7 vaccine in combination with active anti-FGF-2 immunization synergistically elicits robust antitumor immunity in mice

Xie, Hanghang; Shu, Congyan; Bai, Hongmei; Sun, Pengyan; Liu, Hongxian; Qi, Jialong; Li, Sijin; Ye, Chao; Gao, Feng; Yuan, Mingcui; Chen, Yongjun; Pan, Manchang; Xu, Yang; Ma, Yanbing

doi:10.1016/j.nano.2020.102254

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…The TC-1 cell line used in this model is derived from C57BL/6 mice and shares genetic similarity with this strain, allowing tumor cells to be transplanted back without triggering immune rejection. Additionally, the TC-1 cell line originated from the transformation of primary lung epithelial cells of C57BL/6 mice with the E6 and E7 oncogenes of papillomavirus type 16 (HPV-16), facilitating tumor formation upon injection into mice [ 45 , 54 ].…”

Section: Resultsmentioning

confidence: 99%

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model

Hernández-Rangel,

Hernandez-Fuentes,

Montes-Galindo

et al. 2024

Biomedicines

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Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.

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Section: Resultsmentioning

confidence: 99%

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model

Hernández-Rangel,

Hernandez-Fuentes,

Montes-Galindo

et al. 2024

Biomedicines

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“…In cervical cancer, a possible correlation between aberrant FGFR signaling and HPV 16 E5 expression has been shown, with HPV16 E5 initiating a switch in isoform expression from FGFR2b to FGFR2c [35]. A recent study demonstrated that a combination of HPV16 E7 vaccine and active immunization against FGF2 can enhance antitumor immune responses in TC‐1 tumors in mice [86]. In addition, HPV oncoproteins E5, E6, and E7 can manipulate signaling pathways such as STATs, that were constitutively active in our cell lines (Fig.…”

Section: Discussionmentioning

confidence: 99%

FGF signalling facilitates cervical cancer progression

et al. 2022

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Cervical cancer is one of the most frequently diagnosed cancers in women worldwide. While cervical cancer is caused by human papillomavirus (HPV), not all females infected with HPV develop the disease, suggesting that other factors might facilitate its progression. Growing evidence supports the involvement of the fibroblast growth factor receptor (FGFR) axis in several cancers, including gynecological. However, for cervical cancer, the molecular mechanisms that underpin the disease remain poorly understood, including the role of FGFR signaling. The aim of this study was to investigate FGF(R) signaling in cervical cancer through bioinformatic analysis of cell line and patient data and through detailed expression profiling, manipulation of the FGFR axis, and downstream phenotypic analysis in cell lines (HeLa, SiHa, and CaSki). Expression (protein and mRNA) analysis demonstrated that FGFR1b/c, FGFR2b/c, FGFR4, FGF2, FGF4, and FGF7 were expressed in all three lines. Interestingly, FGFR1 and 2 localized to the nucleus, supporting that nuclear FGFRs could act as transcription factors. Importantly, 2D and 3D cell cultures demonstrated that FGFR activation can facilitate cell functions correlated with invasive disease. Collectively, this study supports an association between FGFR signaling and cervical cancer progression, laying the foundations for the development of therapeutic approaches targeting FGFR in this disease.

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“…To develop a peptide vaccine, a highly immunogenic and targeted delivery system is particularly important . Nanoscale vaccines have been reported to be highly immunogenic, and a variety of nanosized carriers have been used for tumor antigen delivery, including hepatitis B core antigen (HBcAg) virus-like particles (VLPs), bacteriophage Qβ protein (Qβ-VLPs), ferritin nanoparticles (NPs), self-assembled nanofibers, bacterial outer membrane vesicles (OMVs), beta-1,3-glucan particles (GPs) derived from Saccharomyces cerevisiae , and self-healing microcapsules . The delivery of a nanoscale carrier is able to improve the stability, uptake efficiency by antigen presenting cells (APCs), lymph node localization, and cross-presentation of tumor peptides, and thus promote antitumor cellular immunity.…”

Section: Introductionmentioning

confidence: 99%

Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform

Zheng

et al. 2023

ACS Nano

Self Cite

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In recent years, virus-derived self-assembled protein nanoparticles (NPs) have emerged as attractive antigen delivery platforms for developing both preventive and therapeutic vaccines. In this study, we exploited the genetically engineered Norovirus S domain (Nov-S) with SpyCatcher003 fused to the C-terminus to develop a robust, modular, and versatile NP-based carrier platform (Nov-S-Catcher003). The NPs can be conveniently armed in a plug-and-play pattern with SpyTag003-linked antigens. Nov-S-Catcher003 was efficiently expressed in Escherichia coli and self-assembled into highly uniform NPs with a purified protein yield of 97.8 mg/L. The NPs presented high stability at different maintained temperatures and after undergoing differing numbers of freeze−thaw cycles. Tumor vaccine candidates were easily obtained by modifying Nov-S-Catcher003 NPs with SpyTag003-linked tumor antigens. Nov-S-Catcher003-antigen NPs significantly promoted the maturation of bone marrow-derived dendritic cells in vitro and were capable of efficiently migrating to lymph nodes in vivo. In TC-1 and B16F10 tumor-bearing mice, the subcutaneous immunization of NPs elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In the TC-1 model, the NPs even completely abolished established tumors. In conclusion, the Nov-S-Catcher003 system is a promising delivery platform for facilitating the development of NP-based cancer vaccines.

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A therapeutic HPV16 E7 vaccine in combination with active anti-FGF-2 immunization synergistically elicits robust antitumor immunity in mice

Cited by 6 publications

References 36 publications

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model

FGF signalling facilitates cervical cancer progression

Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform

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