Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells

Rabu, Catherine; Rangan, Laurie; Florenceau, Laetitia; Fortun, Agnès; Charpentier, Maud; Dupré, Émilie; Paolini, Léa; Beauvillain, Céline; Dupel, E; Latouche, Jean-Baptiste; Adotévi, Olivier; Labarrière, Nathalie; Lang, François

doi:10.1080/2162402x.2018.1560919

Cited by 34 publications

(27 citation statements)

References 28 publications

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“…In addition, CD4 + T cells also exhibit direct antitumor effector function ( 57 ). Therefore, the artificial elongation of tumor-associated CD8 + Tcell epitopes or the application of multivalent long peptides comprising at the same time CD4 + and CD8 + T cell epitopes displays promising attempts to improve the efficacy and clinical outcome of peptide vaccination ( 58 , 59 , 60 , 61 , 62 , 63 ). The enhanced induction of T cell responses with long vaccine peptides could also be explained by the fact that exact epitopes bind directly to HLA class I molecules of any somatic cell and thus also to nonprofessional antigen-presenting cells (APCs) without further processing, which could then lead to suboptimal T cell priming and induce T cell tolerance ( 51 , 64 , 65 ).…”

Section: Antigen Selection—the Devil Is In the Detailsmentioning

confidence: 99%

The Peptide Vaccine of the Future

Nelde

Rammensee

Walz

2021

Molecular & Cellular Proteomics

118

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The approach of peptide-based anti-cancer vaccination has proven the ability to induce cancer-specific immune responses in multiple studies for various cancer entities. However, clinical responses remain so far limited to single patients and broad clinical applicability was not achieved. Therefore, further efforts are required to improve peptide vaccination in order to integrate this low side effect therapy into the clinical routine of cancer therapy. To design clinically effective peptide vaccines in the future, different issues have to be addressed and optimized comprising antigen target selection as well as choice of optimal adjuvants and vaccination schedules. Furthermore, the combination of peptide-based vaccines with other immuno- and molecular targeted therapies as well as the development of predictive biomarkers could further improve efficacy. In this review, current approaches in the development of peptide-based vaccines and critical implications for optimal vaccine design are discussed.

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Section: Antigen Selection—the Devil Is In the Detailsmentioning

confidence: 99%

The Peptide Vaccine of the Future

Nelde

Rammensee

Walz

2021

Molecular & Cellular Proteomics

118

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“…Recently SLPs derived from MELOE-1 melanoma antigen have been developed from Class I and Class II epitopes separated by a cathepsin protease-sensitive linker ( 62 ). Cathepsins are key proteases in dendritic cells involved in antigen presentation ( 63 , 64 ), and it was found that the composition and size of the Cathepsin-sensitive linker had a significant impact on the presentation of the CD4 + and CD8 + T cell epitopes.…”

Section: Designing Peptide-based Cancer Vaccinesmentioning

confidence: 99%

“…Cathepsins are key proteases in dendritic cells involved in antigen presentation ( 63 , 64 ), and it was found that the composition and size of the Cathepsin-sensitive linker had a significant impact on the presentation of the CD4 + and CD8 + T cell epitopes. Of the linker sequences tested, LLSVGG showed the strongest immunogenicity ( 62 ). Mouse studies to evaluate SLPs in the prime-boost immunisation strategy using LLSVGG-based vaccine showed a strong CD8 + T cell response, but a lower CD4 + compared to human PBMC tests, which could produce a less well-rounded response, and shows the epitope sensitivity differences between mice and human models ( 62 ).…”

Section: Designing Peptide-based Cancer Vaccinesmentioning

confidence: 99%

“…Of the linker sequences tested, LLSVGG showed the strongest immunogenicity ( 62 ). Mouse studies to evaluate SLPs in the prime-boost immunisation strategy using LLSVGG-based vaccine showed a strong CD8 + T cell response, but a lower CD4 + compared to human PBMC tests, which could produce a less well-rounded response, and shows the epitope sensitivity differences between mice and human models ( 62 ). Mouse tumour models also revealed a reduction in tumour growth in 4 out of 7 mice when compared to unvaccinated mice but fell outside of significance ( 62 ).…”

Section: Designing Peptide-based Cancer Vaccinesmentioning

confidence: 99%

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Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines

2021

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Peptide-based cancer vaccines rely upon the strong activation of the adaptive immune response to elicit its effector function. They have shown to be highly specific and safe, but have yet to prove themselves as an efficacious treatment for cancer in the clinic. This is for a variety of reasons, including tumour heterogeneity, self-tolerance, and immune suppression. Importance has been placed on the overall design of peptide-based cancer vaccines, which have evolved from simple peptide derivatives of a cancer antigen, to complex drugs; incorporating overlapping regions, conjugates, and delivery systems to target and stimulate different components of antigen presenting cells, and to bolster antigen cross-presentation. Peptide-based cancer vaccines are increasingly becoming more personalised to an individual’s tumour antigen repertoire and are often combined with existing cancer treatments. This strategy ultimately aids in combating the shortcomings of a more generalised vaccine strategy and provides a comprehensive treatment, taking into consideration cancer cell variability and its ability to avoid immune interrogation.

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“…The optimal peptide length for therapeutic cancer vaccines has been identified in preclinical and clinical studies. Short peptides of ∼ 8-11 amino acids (a.a.) are the typical CD8 + T-cell epitopes while long peptides of ∼ 15-32 a.a. contain both CD8 + and CD4 + Tcell epitopes (6,7). Neoantigenic epitopes can be predicted based on their sequence, expression, proteasome cleavage, peptide abundance, MHC-binding affinity and other physiochemical and structural features of peptide-MHC complexes.…”

Section: Introductionmentioning

confidence: 99%

Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma

Mohsen

Speiser

Michaux

et al. 2021

Preprint

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Background: Harnessing the immune system to purposely recognize and destroy tumours represents a significant breakthrough in clinical oncology. Nonsynonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies including cancer vaccines as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multi-target vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform. Methods: Here we identified mutations of murine mammary carcinoma cells by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click-chemistry method for easy preparation of vaccines against mouse mammary carcinoma. Results: As compared to short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells which readily produced IFN-γ and TNF-α. The resulting anti-tumour effect was associated with favourable immune re-polarization in the tumour microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumour recurrence and metastases, and prolonged mouse survival, despite the tumour's low mutational burden. Conclusion: Integrating mass spectrometry-based immunopeptidomics and whole exome-sequencing is an efficient technique for identifying neoantigenic peptides. A multi-target VLP-based vaccine shows a promising anti-tumour results in an aggressive murine mammary carcinoma cell line. Future clinical application using this strategy is readily feasible and practical, as click-chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.

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Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells

Abstract: Lang (2019) Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells, OncoImmunology, 8:4, e1560919,

Cited by 34 publications

References 28 publications

The Peptide Vaccine of the Future

The Peptide Vaccine of the Future

Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines

Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma

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