Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice

Gómez-Gutiérrez, Jorge G.; Elpek, Kutlu G.; Oca‐Luna, Roberto Montes de; Shirwan, Haval; Zhou, Huiyun; McMasters, Kelly M.

doi:10.1007/s00262-006-0247-2

Cited by 76 publications

(62 citation statements)

References 55 publications

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“…The fusion of calreticulin with HPV-16 E7 can stimulate CD8 + cytotoxic T-lymphocytes, resulting in a strong antitumor immune response. This approach has been tested in several vectors such as DNA vaccine, vaccinia virus, and adenovirus with promising results (12,(15)(16)(17)(18)(19)(20)(21)(22).…”

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confidence: 98%

Enhancement of Ad-CRT/E7-Mediated Antitumor Effect by Preimmunization withL. lactisExpressing HPV-16 E7

et al. 2014

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Although current polyvalent vaccines can prevent development of cervical cancer, they cannot be used to treat patients who already have the disease. Adenovirus expressing calreticulin-E7 (Ad-CRT-E7) has shown promising results in the cervical cancer murine model. We also demonstrated that immunization with Lactococcus lactis encoding HPV-16 E7 (Ll-E7) anchored to its surface induces significant HPV-16 E7-specific immune response. Here, we assessed the combination of both approaches in the treatment of a cervical cancer animal model. Intranasal preimmunization of Ll-E7, followed by a single Ad-CRT/E7 application, induced ∼80% of tumor suppression in comparison with controls. Mice treated with a combination of Ll-E7 and Ad-CRT/E7 resulted in a 70% survival rate 300 days post-treatment, whereas 100% of the mice in the control groups died by 50 days. Significant CD8+ cytotoxic T-lymphocytes infiltration was detected in the tumors of mice treated with Ll-E7+Ad-CRT/E7. Tumors with regression showed a greater number of positive cells for in situ TUNEL staining than controls. Our results suggest that preimmunization with Ll-E7 enhances the Ad-CRT/E7-mediated antitumor effect. This treatment provides an enormous advantage over repeated applications of Ad-CRT/E7 by maintaining the effectiveness of the three-dose application of Ad-CRT/E7, but avoiding the high systemic toxicities associated with such repeat treatments.

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confidence: 98%

Enhancement of Ad-CRT/E7-Mediated Antitumor Effect by Preimmunization withL. lactisExpressing HPV-16 E7

et al. 2014

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“…Using the human papillomavirus (HPV) type 16 E7 protein, HSP70 was shown to elicit a CTL response, though no anti-tumor activity was generated with HSP110 [25]. Studying this same HPV protein, vaccination with an adenoviral vector expressing calreticulin-E7 fusion protein was effective in preventing E7-expressing tumor growth [26].…”

Section: Heat Shock Proteinsmentioning

confidence: 97%

Heat shock protein-peptide complex-96 (Vitespen) for the treatment of cancer

Amato

2008

Oncol Rev

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Heat shock proteins (HSPs) are the most abundant and ubiquitous soluble intracellular proteins. Members of the HSP family bind peptides, they include antigenic peptides generated within cells. HSPs also interact with antigen-presenting cells (APCs) through CD91 and other receptors, eliciting a cascade of events that includes re-presentation of HSP-chaperoned peptides by major histocompatability complex (MHC), translocation of nuclear factorkappaB (NFkB) into the nuclei, and maturation of dendritic cells (DCs). These consequences point to a key role of heat shock proteins in fundamental immunological phenomena such as activation of APCs, indirect presentation (or crosspriming) of antigenic peptides, and chaperoning of peptides during antigen presentation. The properties of HSPs also allow them to be used for immunotherapy of cancers and infections in novel ways. This paper reviews the development and clinical trial progress of vitespen, an HSP peptide complex vaccine based on tumor-derived glycoprotein 96.

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“…DOI: 10.3109/10717544.2013.801534 feasible option in therapeutic HPV vaccines (Lin et al, 2010). The Viruses include adenovirus (Gomez-Gutierrez et al, 2007), adeno-associated virus (Jin et al, 2005), vaccinia virus (Lamikanra et al, 2001) and alphaviruses (Cassetti et al, 2004). The tumor cells may express different levels of antigenic peptides loaded by class I MHC molecule.…”

Section: Discussionmentioning

confidence: 99%

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers

et al. 2013

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The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal of gp96] and compared their immunogenicity and protective effects in C57BL/6 mice against TC-1 challenge. TC-1 murine model is primary C57BL/6 mice lung epithelial cells co-transformed with HPV16 E6, HPV16 E7 and ras oncogenes. Our results showed that subcutaneous administration of mice with both the recombinant L.tar-E7-NT

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Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice

Abstract: Vaccination with an adenoviral vector expressing CRT-E7 fusion protein represents an effective strategy for immunotherapy of cervical cancer in rodents, with possible therapeutic potential in clinical settings.

Cited by 76 publications

References 55 publications

Enhancement of Ad-CRT/E7-Mediated Antitumor Effect by Preimmunization withL. lactisExpressing HPV-16 E7

Enhancement of Ad-CRT/E7-Mediated Antitumor Effect by Preimmunization withL. lactisExpressing HPV-16 E7

Heat shock protein-peptide complex-96 (Vitespen) for the treatment of cancer

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers

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