Topic
HspE7
About: HspE7 is a research topic. Over the lifetime, 12 publications have been published within this topic receiving 666 citations.
Papers
TL;DR: In vitro analyses indicated that immunization with hspE7 leads to the induction of a Th1‐like cell‐mediated immune response based on the pattern of secreted cytokines and the presence of cytolytic activity following antigenic recall, and in vivo studies demonstrate that tumour regression following therapeutic hSpE7 immunization is CD8‐dependent and CD4‐independent.
Abstract: Human papillomavirus type 16 (HPV16) infection has been linked to the development of cervical and anal dysplasia and cancer. One hallmark of persistent infection is the synthesis of the viral E7 protein in cervical epithelial cells. The expression of E7 in dysplastic and transformed cells and its recognition by the immune system as a foreign antigen make it an ideal target for immunotherapy. Utilizing the E7-expressing murine tumour cell line, TC-1, as a model of cervical carcinoma, an immunotherapy based on the administration of an adjuvant-free fusion protein comprising Mycobacterium bovis BCG heat shock protein (hsp)65 linked to HPV16 E7 (hspE7) has been developed. The data show that prophylactic immunization with hspE7 protects mice against challenge with TC-1 cells and that these tumour-free animals are also protected against re-challenge with TC-1 cells. In addition, therapeutic immunization with hspE7 induces regression of palpable tumours, confers protection against tumour re-challenge and is associated with long-term survival (> 253 days). In vitro analyses indicated that immunization with hspE7 leads to the induction of a Th1-like cell-mediated immune response based on the pattern of secreted cytokines and the presence of cytolytic activity following antigenic recall. In vivo studies using mice with targeted mutations in CD8 or MHC class II or depleted of CD8 or CD4 lymphocyte subsets demonstrate that tumour regression following therapeutic hspE7 immunization is CD8-dependent and CD4-independent. These studies extend previous observations on the induction of cytotoxic T lymphocytes by hsp fusion proteins and are consistent with the clinical application of hspE7 as an immunotherapy for human cervical and anal dysplasia and cancer.
204 citations
TL;DR: HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity and a larger randomized, controlled trial is needed to better define efficacy.
163 citations
TL;DR: A retrospective review of patients’ medical records suggests that HspE7 may be broadly active in anogenital warts, which crosses multiple human papillomavirus types and improved substantially but usually did not totally disappear within six months.
Abstract: PURPOSE: Human papillomavirus causes anogenital squamous intraepithelial lesions, warts, and cancer Treatment of squamous intraepithelial lesions to prevent cancer often requires extensive surgery We tested a human papillomavirus-specific immunotherapy, HspE7, as a potential alternative METHODS: HspE7 was constructed by fusing heat shock protein Hsp65 from bacille Calmette-Guerin to E7 protein from human papillomavirus-16 Improvement in pathologic diagnosis of patients with persistent high-grade squamous intraepithelial lesions was studied in an open-label trial (HspE7 500 μg monthly ×3) Anogenital warts were not a trial parameter, but a retrospective review of the medical records of the first 22 patients enrolled at one site was undertaken to estimate the quality and frequency of responses of anogenital warts Patients with warts by physical examination at baseline were scored at 24 weeks as to the percent reduction in wart size RESULTS: Fourteen of the 22 patients had warts at baseline At Week 24, 3 of the 14 patients had complete resolution of their warts, and 10 had warts reduced in size an estimated 70 to 95 percent The remaining patient’s warts increased in size The reduction in size in most patients greatly diminished the procedure necessary for complete ablation No serious or severe adverse events were related to HspE7 CONCLUSIONS: A retrospective review of patients’ medical records suggests that HspE7 may be broadly active in anogenital warts This activity crosses multiple human papillomavirus types The warts improved substantially but usually did not totally disappear within six months Patient follow-up continues A new randomized, placebo-controlled trial is underway to evaluate these findings
105 citations
TL;DR: SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity, and three of five participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response.
Abstract: OBJECTIVES To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. DESIGN A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. SETTING University-based research clinic. PARTICIPANTS Thirteen HIV-positive men and two HIV-positive women with HG-AIN. RESULTS There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). CONCLUSIONS SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.
94 citations
TL;DR: The evidence supporting each of these adjuncts varies with a majority having only case reports or cases-series to support their use, but there is hope on the horizon with regard to the HPV vaccine and its potential to prevent future transmission of this disease.
Abstract: Background: Recurrent respiratory papillomatosis is caused by the human papillomavirus types (HPV) 6 and 11. It affects both children and adults. In a small number of cases, the disease can be very aggressive causing significant morbidity and possibly death. Surgical therapy is the primary treatment but in patients with aggressive disease, adjunctive therapy is initiated. The majority of these adjuncts center on immunomodulation, disruption of molecular signaling cascades or interruption of viral replication to help decrease the severity of the disease. Recently, a preventative vaccine has become available but data on its effectiveness will be at least a decade away. In the mean time, researchers are examining other vaccination strategies in the fight against HPV disease. Objective: We will review the following pharmacotherapies used in the adjunct treatment of RRP: interferon, acyclovir, ribivirin, cidofovir, COX-2 inhibitors, retinoids, anti-reflux medications, zinc, indole-3-carbinol, therapeutic/preve...
51 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2017 | 1 |
| 2010 | 1 |
| 2009 | 2 |
| 2007 | 1 |
| 2006 | 1 |
| 2005 | 1 |