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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.

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

Authors :
Daradoumis J
Müller MD
Neckermann P
Asbach B
Schrödel S
Thirion C
Wagner R
Thor Straten P
Holst PJ
Boilesen D
Source :
Cancers [Cancers (Basel)] 2023 Dec 15; Vol. 15 (24). Date of Electronic Publication: 2023 Dec 15.
Publication Year :
2023

Abstract

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.

Details

Language :
English
ISSN :
2072-6694
Volume :
15
Issue :
24
Database :
MEDLINE
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
38136407
Full Text :
https://doi.org/10.3390/cancers15245863