Induction of Antitumor Immunity Against Cervical Cancer by Protein HPV-16 E7 in Fusion With Ricin B Chain in Tumor-Bearing Mice

Sadraeian, Mohammad; Rasoul‐Amini, Sara; Mansoorkhani, Mohammad Javad Khoshnood; Mohkam, Milad; Ghoshoon, Mohammad Bagher; Ghasemi, Younes

doi:10.1097/igc.0b013e3182907989

Cited by 23 publications

(13 citation statements)

References 22 publications

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“…To design potent HPV vaccines, the best tumor antigens should be combined with the most effective immunogens/adjuvants or delivery systems to achieve positive clinical results. For immunotherapy of HPV16-associated cervical cancers, the E7 protein is considered as a promising candidate (14). The use of adjuvants has been demonstrated to be crucial for enhancement of the potency of E7-based therapeutic vaccines (15).…”

Section: Introductionmentioning

confidence: 99%

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

et al. 2016

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Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPVassociated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/ Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h posttransfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-c levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines. V C 2016 IUBMB Life, 68(6): [459][460][461][462][463][464][465][466][467] 2016

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Section: Introductionmentioning

confidence: 99%

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

et al. 2016

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“…Manipulating the uptake of antigens by dendritic cells directly in vivo, or ex vivo before reinfusion into the patient, to produce strong antitumor immune responses has become a major area of research in immunotherapy. Among the toxins used for these studies are DT, Pseudomonas exotoxin A, the adenylate cyclase from B. pertussis, Shiga toxin, pertussis toxin, anthrax toxin [98] (and also the plant toxin ricin [99][100][101], and the insect toxin phospholipase A 2 from bee venom [102,103]. In most studies, the antigenic peptides or protein fragments are fused to the C domain (or A chain) of the toxin.…”

Section: Delivery Of Peptide or Protein Antigens To Dendritic Cells Fmentioning

confidence: 99%

Engineering of bacterial toxins for research and medicine

Barbier

Gillet

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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“…Other delivery vectors for E6 and E7 peptides include Semliki Forest virus (combined with low‐dose irradiation) , Listeria , lentiviruses , fusions with heat shock proteins , ricin B chain , Shiga toxin B subunit and synthetic polymers . Several studies have examined E6 or E7 DNA vaccines combined with various adjuvants .…”

Section: Therapeutic Vaccinesmentioning

confidence: 99%

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against highrisk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd. INTRODUCTIONTargeting cancers for immunotherapy is often complicated by a lack of immunogenic tumour peptides. Mutated or overexpressed self-antigens are frequently the targets and invoke a generally low affinity/avidity T and B cell response. In contrast, the tight association between infection with HPV and cervical cancer means that foreign viral proteins encoded by HPV can provide the basis of either prophylactic or therapeutic cancer vaccines [1,2]. The natural course of anogenital HPV infection results in overwhelming clearance of the virus in 98% of individuals with an immune component suggested by the increased risk of HPV-associated cancers in immune-compromised organ transplant recipients [3,4]. However, HPV genotype-specific antibodies against the viral capsid proteins (L1 and L2) are produced at only low levels in about half the patients, can take close to a year to develop after natural infection and associate with higher viral loads in the cervix [5]. Thus, natural antibody may reflect the non-lytic, localised, intracellular nature of the infection leading to poor immunogenicity for immunoglobulin production and a greater emphasis on T-cell immunity for viral clearance. In contrast, prior immunization with HPV capsid proteins in animal studies induces high titres of antibody that are protective against challenge infection. Early studies in dogs demonstrated that prior immunization with L1 capsid protein could protect beagles from mucosal challenge with canine oral ...

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Induction of Antitumor Immunity Against Cervical Cancer by Protein HPV-16 E7 in Fusion With Ricin B Chain in Tumor-Bearing Mice

Abstract: We concluded that immunization with E7-RTB protein without any adjuvant could generate antitumor effects in mice challenged with TC-1 cells. This research verifies the clinical applications and the future prospects for development of HPV-16 E7 therapeutic vaccines fused to immunoadjuvants.

Cited by 23 publications

References 22 publications

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

Engineering of bacterial toxins for research and medicine

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

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