Dataset Information

Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication.

ABSTRACT:

Background

Despite considerable efforts at developing therapeutic vaccines for cancer, clinical translation of preclinical successes has been challenging, largely due to the difficulty of inducing strong and sustained cytotoxic T lymphocyte (CTL) responses in patients. Several peptide-based cancer vaccines have failed to show sustainable tumor regression in the clinic, possibly because of a lack of optimization of both the adjuvant and antigen components of the preparations. Here, we aimed to develop and optimize a vaccine format utilizing a synthetic long peptide (SLP) containing the human papilloma virus 16 (HPV16) E7 antigen, with a centrally located defined MHC class I epitope, and evaluate its immunogenicity and efficacy in combination with various adjuvant formulations.

Methods

E7_31-73 SLP was tested alone or in combination with toll-like receptor (TLR)3, TLR4, TLR7/8 and TLR9 agonists and formulated in oil-in-water (o/w) or water-in-oil (w/o) emulsions to determine a vaccine format inducing a robust CD8 T cell response in murine models. Once a lead vaccine format was determined, we examined its ability to inhibit tumor growth in the murine TC-1 model that expresses HPV16 E7 antigen.

Results

We identified the TLR9 agonist CpG formulated in a squalene-based o/w emulsion as the most potent adjuvant, inducing the expansion of multifunctional antigen specific CD8 T cells with cytolytic potential. We also demonstrated that SLP E7_31-73?+?CpG?+?o/w emulsion vaccine can provide prophylactic and more importantly, therapeutic benefit in the TC-1 murine tumor model.

Conclusions

Our results demonstrate that the novel vaccine format E7 SLP?+?CpG delivered in an o/w emulsion holds potential for the promotion of strong CTL responses and tumor eradication and encourages further development of peptide/adjuvant vaccines in cancer immunotherapy strategies.

SUBMITTER: Maynard SK

PROVIDER: S-EPMC6555006 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication.

Maynard Sean K SK Marshall Jason D JD MacGill Randall S RS Yu Li L Cann Jennifer A JA Cheng Lily I LI McCarthy Michael P MP Cayatte Corinne C Robbins Scott H SH

BMC cancer 20190606 1

<h4>Background</h4>Despite considerable efforts at developing therapeutic vaccines for cancer, clinical translation of preclinical successes has been challenging, largely due to the difficulty of inducing strong and sustained cytotoxic T lymphocyte (CTL) responses in patients. Several peptide-based cancer vaccines have failed to show sustainable tumor regression in the clinic, possibly because of a lack of optimization of both the adjuvant and antigen components of the preparations. Here, we aim ...[more]

PMID: 31170937

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Project description:Background:Application of topical moisturizers is an essential part of the management of atopic dermatitis (AD). Linoleic acid (LA), the most abundant fatty acid in the epidermis, and its derivatives have an essential role in the structure and function of the epidermal barrier, and their defects are prominent in AD. The aim of this study was to compare the efficacy and safety of two cosmetic products containing either LA or urea in patients with AD. Patients and methods:A total of 20 patients with AD who met the eligibility criteria and provided written informed consents were enrolled in this randomized, intra-individual split-body, single-center trial. Symmetrical lesions of patients were randomized for treatment with LA- or urea-containing water-in-oil (w/o) emulsions applied two to three times daily for 4 weeks. The efficacy of the two products was evaluated by local Scoring Atopic Dermatitis (SCORAD) of both lesions and also patient (or guardian) satisfaction. In addition, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, pH, sebum, temperature, erythema, melanin content, and ultrasonographic thickness and echo density of epidermis and dermis were measured before, and 2 and 4 weeks after, treatment. Results:Four weeks of treatment with the LA-containing product resulted in a significant decrease in local SCORAD, TEWL, erythema, and echo density of dermis, as well as an increase in SC hydration compared to baseline. The urea-containing product also reduced the local SCO-RAD and echo density of dermis and increased SC hydration. In contrast to the LA-containing product, changes in TEWL and erythema were not significant. Moreover, the reduction of erythema was significantly higher in the LA-containing product-treated side compared to the urea-containing product-treated side (p = 0.006). Conclusion:Both LA- or urea-containing w/o emulsions can significantly improve barrier dysfunction and clinical severity of AD. In agreement with literature, it was confirmed that an LA-containing w/o emulsion exhibited erythema-reducing effects. Since emollients should be used on a regular basis, patients should choose a product by individual preference following recommendation by their dermatologists.

Dataset Information

Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication.

Background

Methods

Results

Conclusions

Publications

Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication.

Similar Datasets

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