Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Xu, Ping; Woodhouse, Isaac; Hancock, Gemma; Parker, Robert; Marx, Kristina; Müller, Julius; Salatino, Silvia; Partridge, Thomas; Nicastri, Annalisa; Liao, Hanqing; Kruppa, Gary; Hellner, Karin; Dorrell, Lucy; Ternette, Nicola

doi:10.1016/j.isci.2023.106101

Cited by 5 publications

(8 citation statements)

References 65 publications

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“…Similarly, Peng et al reported an E1 expression in all enrolled cervical cancer patients. Together, this indicates the advantages of the inclusion of E1 and E2 in addition to E6 and E7 in therapeutic HPV vaccine designs [19]. Notably, it has been shown in cervical cancer patients that detection, even of low frequencies of E1-specific T cells, correlated with a dramatic improvement in progression-free survival [41].…”

Section: Discussionmentioning

confidence: 95%

“…We have previously shown that such a vaccine design is capable of inducing strong T-cell responses in outbred mouse strains and have seen indications that E1-specific T cells may enhance tumor control in C57BL/6 mice. The use of E1 and E2 as targets for HPV therapeutic vaccines is also supported by recent studies on patients with cervical cancer or OPSCC [18][19][20].…”

Section: Introductionmentioning

confidence: 94%

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Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen

Daradoumis,

Müller,

Neckermann

et al. 2023

Cancers

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Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 94%

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen

Daradoumis,

Müller,

Neckermann

et al. 2023

Cancers

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show abstract

“…By whole-genome sequencing (WGS) and whole-exome sequencing (WES), sample-specific mutations, including single-nucleotide variants (SNVs), 18 insertion-deletion (in-del) frameshifts, 19,20 and onco-viral sequences can be obtained. 21,22 RNA sequencing (RNA-seq) and long-read sequencing F I G U R E 2 Presentation machinery for class I immunopeptides at a glance: from genomic blueprint to T cell recognition. Successful transcription without nonsense-mediated decay (NMD) is the first barrier for somatic mutation-carrying immunopeptides.…”

Section: Inextricable Link Between Deep Nucleic Acid-sequencing Techn...mentioning

confidence: 99%

“…To find a cancer‐specific antigen, it is inevitable to interrogate the individual genomic/transcriptomic information and incorporate the cancer specific sequences into personalized/customized database for peptide search. By whole‐genome sequencing (WGS) and whole‐exome sequencing (WES), sample‐specific mutations, including single‐nucleotide variants (SNVs), 18 insertion–deletion (in‐del) frameshifts, 19,20 and onco‐viral sequences can be obtained 21,22 . RNA sequencing (RNA‐seq) and long‐read sequencing can provide the transcription information of NCPs for immunopeptides.…”

Section: Transformative Technologies That Shed Light Upon the Dark Ma...mentioning

confidence: 99%

“…By whole‐genome sequencing (WGS) and whole‐exome sequencing (WES), sample‐specific mutations, including single‐nucleotide variants (SNVs), 18 insertion–deletion (in‐del) frameshifts, 19 , 20 and onco‐viral sequences can be obtained. 21 , 22 RNA sequencing (RNA‐seq) and long‐read sequencing can provide the transcription information of NCPs for immunopeptides. These sources for immunopeptides and supporting sequencing technologies were well summarized in the previous reviews.…”

Section: Transformative Technologies That Shed Light Upon the Dark Ma...mentioning

confidence: 99%

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Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy

Minegishi,

Haga,

Ueda

2024

Cancer Science

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With significant advances in analytical technologies, research in the field of cancer immunotherapy, such as adoptive T cell therapy, cancer vaccine, and immune checkpoint blockade (ICB), is currently gaining tremendous momentum. Since the efficacy of cancer immunotherapy is recognized only by a minority of patients, more potent tumor‐specific antigens (TSAs, also known as neoantigens) and predictive markers for treatment response are of great interest. In cancer immunity, immunopeptides, presented by human leukocyte antigen (HLA) class I, play a role as initiating mediators of immunogenicity. The latest advancement in the interdisciplinary multiomics approach has rapidly enlightened us about the identity of the “dark matter” of cancer and the associated immunopeptides. In this field, mass spectrometry (MS) is a viable option to select because of the naturally processed and actually presented TSA candidates in order to grasp the whole picture of the immunopeptidome. In the past few years the search space has been enlarged by the multiomics approach, the sensitivity of mass spectrometers has been improved, and deep/machine‐learning‐supported peptide search algorithms have taken immunopeptidomics to the next level. In this review, along with the introduction of key technical advancements in immunopeptidomics, the potential and further directions of immunopeptidomics will be reviewed from the perspective of cancer immunotherapy.

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How mass spectrometric interrogation of MHC class I ligandomes has advanced our understanding of immune responses to viruses

Ternette

Adamopoulou

Purcell

2023

Seminars in Immunology

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Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Cited by 5 publications

References 65 publications

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen

Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy

How mass spectrometric interrogation of MHC class I ligandomes has advanced our understanding of immune responses to viruses

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