Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7

Tsang, Kwong Y.; Fantini, Massimo; Fernando, Romaine I.; Palena, Claudia; David, Justin M.; Hodge, James W.; Gabitzsch, Elizabeth S.; Jones, Frank R.; Schlom, Jeffrey

doi:10.1016/j.vaccine.2017.03.025

Cited by 17 publications

(15 citation statements)

References 43 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies have focused on enhancing immunogenicity using immune stimulating agents or adjuvants to avoid this problem. Another solution is the use of agonist epitopes [ 94 ]. Epitope immunogenicity is a crucial factor in vaccine development.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

Panahi¹,

Bolhassani²,

Javadi³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.

show abstract

Section: Discussionmentioning

confidence: 99%

“…A large number of previous studies have used in silico analyses for epitope prediction against different pathogens [ 94 , 96 , 98 – 103 ]. However, the prediction of T cell epitopes inducing strong responses has remained a big challenge.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

Panahi¹,

Bolhassani²,

Javadi³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…They introduced 14 peptides (9 to 43 amino acids) which can be used as potent regions in therapeutic vaccines (Singh et al 2016). Tsang et al analyzed HPV16 E6 and E7 proteins and found six immunogenic epitopes, as well (Tsang et al 2017). While the oncogenic activities of E6 and E7 were well known, the role of E5 is still rather unclear.…”

Section: Discussionmentioning

confidence: 99%

Development of HPV16,18,31,45 E5 and E7 peptides-based vaccines predicted by immunoinformatics tools

et al. 2020

View full text Add to dashboard Cite

Objectives Viral oncoproteins are ideal targets in therapeutic vaccines for functional inhibition of human papillomaviruses (HPVs). Herein, we designed the peptide constructs derived from E5 and E7 oncoproteins of high-risk HPV types 16, 18, 31 and 45 using the bioinformatics tools and investigated their potency in mice. Results The framework of the combined in silico/ in vivo analysis included (1) to determine physicochemical properties of the designed constructs, (2) to identify potential IFN-c-inducing epitopes, (3) to assess allergenicity, (4) to recognize linear and discontinuous B cell epitopes using modeling and validation of 3D structure of the designed constructs, and (5) to evaluate immune responses and tumor growth in vivo. Our in silico data determined high potency of the HPV 16,18,31,45 E5 and HPV 16,18,31,45 E7 peptides for trigger B-and T-cell responses, and IFN-c secretion. In vivo study indicated that the mixture of E5 and E7 immunodominant peptides from four types of high-risk HPV could induce Th1 immune response, and protect completely mice against TC-1 tumor cells. Conclusion Generally, the combined in silico/ in vivo approaches showed the ability of the designed E5 and E7 peptide constructs from four major highrisk HPV types for development of therapeutic vaccines.

show abstract

“…For T2 cells, 3-35 μM of recombinant β2M was also added. As a control, the well-characterized peptide YMLDLQPET (YML) (66) derived from the E7 protein expressed by HPV-16 was used.…”

Section: Screening Of Phage Scfv Specific For Ebv-lmp2(clg)/hla-a0201mentioning

confidence: 99%

TCR-mimic bispecific antibodies targeting LMP2A show potent activity against EBV malignancies

et al. 2018

View full text Add to dashboard Cite

EBV infection is associated with a number of malignancies of clinical unmet need, including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and posttransplant lymphoproliferative disease (PTLD), all of which express the EBV protein latent membrane protein 2A (LMP2A), an antigen that is difficult to target by conventional antibody approaches. To overcome this, we utilized phage display technology and a structure-guided selection strategy to generate human T cell receptor-like (TCR-like) monoclonal antibodies with exquisite specificity for the LMP2A-derived nonamer peptide, C426LGGLLTMV434 (CLG), as presented on HLA-A*02:01. Our lead construct, clone 38, closely mimics the native binding mode of a TCR, recognizing residues at position P3-P8 of the CLG peptide. To enhance antitumor potency, we constructed dimeric T cell engaging bispecific antibodies (DiBsAb) of clone 38 and an affinity-matured version clone 38-2. Both DiBsAb showed potent antitumor properties in vitro and in immunodeficient mice implanted with EBV transformed B lymphoblastoid cell lines and human T cell effectors. Clone 38 DiBsAb showed a stronger safety profile compared with its affinity-matured variant, with no activity against EBV- tumor cell lines and a panel of normal tissues, and was less cross-reactive against HLA-A*02:01 cells pulsed with a panel of CLG-like peptides predicted from a proteomic analysis. Clone 38 was also shown to recognize the CLG peptide on other HLA-A*02 suballeles, including HLA-A*02:02, HLA-A*02:04, and HLA-A*02:06, allowing for its potential use in additional populations. Clone 38 DiBsAb is a lead candidate to treat EBV malignancies with one of the strongest safety profiles documented for TCR-like mAbs.

show abstract

Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7

Cited by 17 publications

References 43 publications

A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

Development of HPV16,18,31,45 E5 and E7 peptides-based vaccines predicted by immunoinformatics tools

TCR-mimic bispecific antibodies targeting LMP2A show potent activity against EBV malignancies

Contact Info

Product

Resources

About