Local mucosal immunization of self-assembled nanofibers elicits robust antitumor effects in an orthotopic model of mouse genital tumors

Li, Sijin; Zhu, Wenbing; Ye, Chao; Sun, Wenjun; Xie, Hanghang; Yang, Xu; Zhang, Qishu; Ma, Yanbing

doi:10.1039/c9nr10334a

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…Recently, Ryan and co-authors demonstrate that STAT1 is an essential mediator of the antitumor response through the inhibition of myeloid derived suppressor cell accumulation and promotion of T-cell mediated immune responses in murine HPV− head and neck squamous cell carcinoma [103]. Many other studies were conducted with the aim to investigate antitumor effects in HPV+ murine models, so Li et al recently published that their candidate vaccine against HPV16E7 significantly reduced Treg and MDSCs infiltration in mouse genital tumors [104,105]. Given the creation of a new immunocompetent mouse model of HPV16+ head and neck squamous cell carcinoma [106], this promising vaccination strategy should be considered and tested for the treatment of HPV+ oropharyngeal SCC.…”

Section: Myeloid Cellsmentioning

confidence: 99%

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

Lechien

Descamps

Seminerio

et al. 2020

Cancers

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Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses.

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Section: Myeloid Cellsmentioning

confidence: 99%

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

Lechien

Descamps

Seminerio

et al. 2020

Cancers

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“…Intravaginal administration is another mucosal immunization route for controlling genital cancer and was demonstrated to be more effective than the subcutaneous route at suppressing orthotopic genital tumor growth. 28 Lee et al demonstrated that the intravaginal administration, but not subcutaneous immunization, of a vaccine containing HPV peptides and flagellin as an adjuvant could suppress orthotopic genital tumor growth and promote the long-term survival of tumor-bearing mice. 29 However, also using an orthotopic genital tumor model, Decrausaz et al reported that subcutaneous immunization of a therapeutic HPV peptide vaccine that included two adjuvants elicited more robust cell-mediated responses compared with mucosal vaccination and promoted the regression of tumors in the genital mucosa.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Orthotopic Genital Cancer Induced by Subcutaneous Administration of Human Papillomavirus Peptide Vaccine with CpG Oligodeoxynucleotides as an Adjuvant in Mice

Wang¹,

Che²,

Yang³

et al. 2021

CMAR

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Persistent high-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer and its precursor lesions. Although prophylactic HPV vaccines have been applied in the general population for the prevention of HPV infections, no licensed therapeutic HPV vaccine is currently available to treat preexisting HPV infections or HPVassociated diseases, including cervical cancer. Materials and Methods: The most common murine cervical cancer model used for the evaluation of the efficacy of a therapeutic HPV vaccine in preclinical studies is the ectopic model, which is established by the subcutaneous inoculation of tumor cells, such as TC-1 cells, into the flank of an animal. We have previously demonstrated the efficacy of a therapeutic HPV peptide vaccine adjuvanted with unmethylated cytosine-phosphateguanosine oligodeoxynucleotide in the clearance of ectopic subcutaneous tumors in C57BL/6 mice after vaccination. In the current study, we established orthotopic genital tumors by injecting TC-1 cells into the vaginal submucosa close to the cervix and assessed whether the subcutaneous administration of the therapeutic vaccine could inhibit the growth of genital tumors. Additionally, we evaluated the effect of the vaccination on the tumor microenvironment. Results: The results showed that the vaccination induced an increase in infiltrating CD4+ and CD8+ T cells, a decrease in myeloid-derived suppressor cells and cancer-associated fibroblasts, as well as the differential expression of a panel of cytokines, chemokines, and matrix metalloproteinases within the tumor microenvironment. Conclusion:The administration of the vaccine resulted in the inhibition of established implanted orthotopic genital tumors by inducing strong antitumor immune responses and reversed tolerogenic local immunosuppression in a mouse model of orthotopic genital cancer.

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“…In a later study, this same vaccine formulation was found to be more effective at suppressing tumor growth when delivered via mucosal immunization, specifically intravaginally, compared to subcutaneously. [ 73 ] Another potential immunotherapy was developed against tumor necrosis factor (TNF) mediated inflammation by covalent modification of Q11 with B‐cell epitope TNF 4‐23 , or CD4+ T cell eptiopes PADRE (aKXVAAWTLKAa, X = cyclohexylalnine) and Vaccinia I1L 7‐21 . [ 74 ] Coassemblies of TNFQ11 with either PADREQ11 or VACQ11 protected mice from TNF‐mediated inflammation, proving the potential of Q11 for various immunotherapies.…”

Section: Applicationsmentioning

confidence: 99%

Multivalent display of chemical signals on self‐assembled peptide scaffolds

et al. 2021

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Self-assembled peptide materials have emerged as promising bioinspired tools for applications that include regenerative medicine, drug delivery, antimicrobial and vaccine development, optics, and catalysis. Peptide self-assembly mediated by noncovalent hydrogen bonding, coulombic, hydrophobic, and aromatic interactions gives rise to a variety of supramolecular structures that reflect on the nature of the constituent peptides. The emergent properties of these supramolecular peptide materials often depend on the multivalent presentation of functional appendages on the self-assembled scaffold. For example, the multivalent display of cell-signaling motifs on self-assembled peptide nanofibrils provides materials that are excellent extracellular matrix mimetics for tissue engineering applications. This review includes a discussion of chemical strategies that address the challenge of appending functional signal motifs in a multivalent display on self-assembled peptide and protein materials. In addition, recent examples of supramolecular peptide materials that rely on the multivalent display of chemical signals for the desired applications are presented. Collectively, this discussion illustrates the potential of self-assembled peptides as sustainable materials to address challenges in contemporary materials science and provides principles for the design of next-generation agents for a variety of applications.

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Local mucosal immunization of self-assembled nanofibers elicits robust antitumor effects in an orthotopic model of mouse genital tumors

Abstract: In this study, we proposed that local mucosal immunization of nanofibers via the intravaginal route represented a promising vaccination strategy for the treatment of genital tumor lesions such as cervical cancer.

Cited by 17 publications

References 40 publications

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

Inhibition of Orthotopic Genital Cancer Induced by Subcutaneous Administration of Human Papillomavirus Peptide Vaccine with CpG Oligodeoxynucleotides as an Adjuvant in Mice

Multivalent display of chemical signals on self‐assembled peptide scaffolds

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