Prevention and treatment of cervical cancer by a single administration of human papillomavirus peptide vaccine with CpG oligodeoxynucleotides as an adjuvant in vivo

Yang, Yang; Che, Yuxin; Zhao, Yan; Wang, Xuelian

doi:10.1016/j.intimp.2019.01.024

Cited by 28 publications

(22 citation statements)

References 40 publications

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“…Our previous studies demonstrated that HPV16 E7 43-77 peptide combined with CpG ODN can induce IFN-γ-producing CD8+ and CD4+ T cells, which contribute to the eradication of small TC-1 grafted tumors in mice. 7 Nevertheless, several challenges remain to use this treatment approach for large tumors. These challenges could be a reflection of poor platforms that fail to elicit optimal DC phagocytosis, antigen processing, or presentation by DCs, or of suboptimal adjuvants.…”

Section: Discussionmentioning

confidence: 99%

“…TC-1 cells were cultured in Roswell Park Memorial Institute 1640 medium supplemented with 10% fetal calf serum, 2 mM G418, 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C under 10% carbon dioxide. 7 Female C57BL/6 mice (6-8 weeks old) were purchased from Liaoning Changsheng Biotechnology Co. Ltd (Benxi, China). Animal care and use were performed according to a protocol reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of China Medical University (IACUC Issue No.…”

Section: Cell Lines and Micementioning

confidence: 99%

“…5,6 In our previous study, we investigated the anti-tumor effect of an HPV peptide vaccine, including CpG oligodeoxynucleotides (CpG ODN) 1826 as an adjuvant and HPV16 E7 43-77 peptide as an antigen, which contains a CD8 T cell epitope (E7 49-57), and two CD4 T cell epitopes (E7 43-77 and E7 50-62). A single administration of the vaccine before and 4 days after inoculation with TC-1 cells expressing HPV16 E6/E7 induced immune responses and resulted in significant prophylactic and therapeutic effects on TC-1 grafted tumors in mice; 7 however, this approach was less successful when used at later stages of tumor growth. Evidence indicated that the surviving tumor cells developed various mechanisms to avoid immune recognition and elimination during tumor progression, offsetting the effects of a theoretically efficient immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice

Zhao

Wang

Yang

et al. 2020

IJN

Self Cite

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Background: Previously, we demonstrated the therapeutic efficacy of a human papillomavirus (HPV) vaccine, including HPV16 E7 peptide and CpG oligodeoxynucleotides (CpG ODN), against small TC-1 grafted tumors. Here, we developed an HPV16 E7 peptide and CpG ODN vaccine delivered using liposomes modified with DC-targeting mannose, Lip E7/CpG, and determined its anti-tumor effects and influence on systemic immune responses and the tumor microenvironment (TME) in a mouse large TC-1 grafted tumor model. Methods: L-alpha-phosphatidyl choline (SPC), cholesterol (CHOL), 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000)] (DSPE-PEG-2000), 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and Mannose-PEG-DSPE, loaded with HPV16 E7 peptide and CpG ODN, were used to construct the Lip E7/CpG vaccine. The anti-tumor effects and potential mechanism of Lip E7/CpG were assessed by assays of tumor growth inhibition, immune cells, in vivo cytotoxic T lymphocyte (CTL) responses and cytokines, chemokines, CD31, Ki67 and p53 expression in the TME. In addition, toxicity of Lip E7/CpG to major organs was evaluated. Results: Lip E7/CpG had a diameter of 122.21±8.37 nm and remained stable at 4°C for 7 days. Co-delivery of HPV16 E7 peptide and CpG ODN by liposomes exerted potent antitumor effects in large (tumor volume ≥200mm 3) TC-1 grafted tumor-bearing mice with inhibition rates of 80% and 78% relative to the control and Free E7/CpG groups, respectively. Vaccination significantly increased numbers of CD4+ and CD8+ T cells, and IFN-γproducing cells in spleens and tumors and enhanced HPV-specific CTL responses, while reducing numbers of inhibitory cells including myeloid-derived suppressor cells and macrophages. Expression of cytokines and chemokines was altered and formation of tumor blood vessels was reduced in the Lip E7/CpG group, indicating possible modulation of the immunosuppressive TME to promote anti-tumor responses. Lip E7/CpG did not cause morphological changes in major organs. Conclusion: Lip E7/CpG induced anti-tumor effects by enhancing cellular immunity and improving tumor-associated immunosuppression. Mannose-modified liposomes are the promising vaccine delivery strategy for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Lines and Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice

Zhao

Wang

Yang

et al. 2020

IJN

Self Cite

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“…[106][107][108] In addition, increased level of IFN-γ helped mediate cellular immunity. 109 Scientists prefer to combine therapeutic vaccines and immune checkpoint inhibitors such as PL-L1 and CTLA-4 in trials. 106,110 Several clinical trials have indicated that therapeutic vaccines plus immune checkpoint inhibitors or radiotherapy together induced an immune response in premalignant lesions and CC.…”

Section: Therapeutic Vaccines and Cytokinesmentioning

confidence: 99%

Cervical Cancer: Emerging Immune Landscape and Treatment

Guo¹,

Hua²

2020

OTT

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Immune cells are essential for defending the body's balance and have increasingly been implicated in controlling tumor growth. In cervical cancer (CC), the immune landscape is extensively connected with human papillomavirus (HPV) status. Recent insights from studies have revealed that as a result of infection with HPV, immune cell populations such as lymphocytes or monocytes change during carcinogenesis. Immune therapy, in particular checkpoint inhibitors, those targeting PD-1 or PD-L1, has shown promising efficacy. This article reviews the immune landscape and immunotherapy of CC.

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“…Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are an effective adjuvant of interest with numerous studies documenting their capabilities for enhancing vaccine efficacies through the activation of both innate and acquired immunities in humans and other animals [ 11 , 12 , 13 , 14 , 15 ]. In this regard, a single immunization with the CpG-adjuvanted human papillomavirus vaccine demonstrated a prophylactic effect in mice by reducing tumor volume and emergence [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Passive Immunity and Antibody Response Induced by Toxoplasma gondii VLP Immunization

et al. 2021

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Passive immunity can provide immediate protection against infectious pathogens. To date, only a few studies have investigated the effect of passive immunization against Toxoplasma gondii, and the use of immune sera acquired from VLP-vaccinated mice for passive immunity assessment remains unreported. In this study, immune sera were produced by a single immunization with virus-like particles (VLPs) expressing the inner membrane complex (IMC), rhoptry protein 18 (ROP18), and microneme protein 8 (MIC8) of Toxoplasma gondii, with or without a CpG-ODN adjuvant. The passive immunization of immune sera conferred protection in mice, as indicated by their potent parasite-specific antibody response, lessened brain cyst counts, lower bodyweight loss, and enhanced survival. In order to confirm that the immune sera of the VLP-immunized mice were truly protective, the antibody responses and other immunological parameters were measured in the VLP-immunized mice. We found that VLP immunization induced higher levels of parasite-specific IgG, IgG subclass, and IgM antibody responses in the sera and intestines than in the controls. Enhanced Th1 and Th2-associated cytokines in the spleen, diminished brain cyst counts, and lessened body weight loss were found following T. gondii ME49 challenge infection. These results suggest that passive immunization with the immune sera acquired from VLP-vaccinated mice can confer adequate protection against T. gondii infection.

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Prevention and treatment of cervical cancer by a single administration of human papillomavirus peptide vaccine with CpG oligodeoxynucleotides as an adjuvant in vivo

Cited by 28 publications

References 40 publications

<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

<p>Cervical Cancer: Emerging Immune Landscape and Treatment</p>

Passive Immunity and Antibody Response Induced by Toxoplasma gondii VLP Immunization

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