Activity of HspE7, a Novel Immunotherapy, in Patients with Anogenital Warts

Goldstone, Stephen E.; Palefsky, Joel M.; Winnett, Mark T.; Neefe, John R.

doi:10.1007/s10350-004-6229-6

Cited by 88 publications

(40 citation statements)

References 14 publications

(13 reference statements)

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“…Similar to results of other HspE7 trials for other HPV-associated neoplasms [21][22][23]30], there was no difference in responses (pathologic or colposcopic) to HspE7 in patients without HPV 16 infection at any visit compared to those who were infected with HPV 16 (22/25 or 88% vs. 23/33 or 70%, p=0.12). Also, there was no difference in the clinical responses of women who were infected with one HPV type compared to those infected with multiple HPV types (data not shown), but this may be due to the small sample size.…”

Section: Response To Treatmentsupporting

confidence: 81%

“…However, future studies using this agent should not restrict patients based on the HPV type. The lack of HPV type-specific treatment efficacy has been reported in other HspE7 trials [22,23,30].…”

Section: Discussionmentioning

confidence: 79%

“…Clinical responses to HspE7 immunotherapy have been observed in children with recurrent respiratory papillomatosis [21] and men and women with genital warts [22] and anal intraepithelial neoplasia (AIN) [23]. Since responses to HspE7 were seen in these other HPV-related diseases, we tested HspE7 in women with CIN III.…”

Section: Introductionmentioning

confidence: 99%

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Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Einstein

Kadish

Burk

et al. 2007

Gynecologic Oncology

129

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Objectives-SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M. bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 E7. This trial was designed to evaluate the efficacy and toxicities of HspE7 in women with CIN III.Methods-HIV (−) women with biopsy-proven CIN III were eligible. Two cohorts were accrued; one cohort to establish efficacy and a second cohort with a longer follow-up period to improve the precision of the trial to estimate response rates. Each patient underwent 3 monthly subcutaneous vaccinations with 500 µg of HspE7 followed by monthly colposcopic follow-up for 1 month in cohort 1 and an extended observation period (2 months) in cohort 2. All patients then underwent a LEEP or cone biopsy of the cervix. A complete pathologic response (pCR) was defined as no evidence of CIN or CIN I (only HPV changes). A partial response (PR) was defined as colposcopic lesion regression of >50% in size. Cervicovaginal lavage samples were obtained at each visit for HPV typing using MY09/ MY11 HPV PCR.Results-Seventy-two patients were registered and screened, of whom 64 were eligible. Fifty-eight patients completed the trial and were evaluable (31 in cohort 1, 27 in cohort 2). There were no significant epidemiologic or HPV type differences between the 2 cohorts so responses were combined for analysis. Of the 58 evaluable patients, 13 (22.5%) had a pCR; 32 (55%) had a PR and 11 (19%) had stable disease. Two (3.5%) patients in cohort 2 had microinvasive disease and were defined as progressive disease. Thirty-three of 58 (57%) of the patients were infected with HPV 16 prior to vaccination or in subsequent visits. There was no significant difference in regression in women infected with HPV 16 compared to those without HPV 16 infection (88% vs. 70%; p=0.12). Women who had a previous LEEP or ablation for CIN were 2.7 times more likely to have a complete response compared to patients without previous treatment, although the difference was not statistically significant (95% CI for rate ratio: 0. 95-6.19, p=0.10). At a cellular level, there was a significant association between local inflammation and response; lower grade of lesional inflammation correlated with a response to HspE7 (p=0.04 using Wilcoxon rank sum test). Conclusions-HspE7 appeared to demonstrate activity in women with CIN III and met a priori assumptions for efficacy; however, it is unclear whether this response was due to natural regression rather than treatment effect. HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity. A larger randomized, controlled trial is needed to better define efficacy and to identify subsets of women most likely to benefit from immunotherapy.

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Section: Response To Treatmentsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 79%

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Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Einstein

Kadish

Burk

et al. 2007

Gynecologic Oncology

129

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“…101, 102 More promising results were obtained with HPV16 E6/E7-derived, synthetic, long peptide vaccines. When tested in a small group of patients with cervical cancer, they caused robust expansion of HPV16 specific CD4ϩ and CD8ϩ T-cells 103 and a recent, nonplacebo controlled, phase II study conducted in women with HPV16 positive high-grade vulvar intraepithelial neoplasia was quite encouraging and induced a robust HPV16 specific immune response as well as very promising clinical responses.…”

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confidence: 99%

Human Papillomaviruses As Therapeutic Targets in Human Cancer

Hellner

Münger

2011

JCO

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A B S T R A C TCervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. HPV oncoproteins contribute to cancer initiation and progression and their expression is necessary for the maintenance of the transformed state. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression, is common to almost all cervical cancers offers unique opportunities for prevention, early detection, and therapy. The potential for prevention has been realized by introduction of prophylactic vaccines that are to prevent transmission of specific high-risk HPVs. Given, however, that these vaccines have no therapeutic efficacy and HPVassociated cervical cancers arise years if not decades after the initial infection, it has been estimated that there will be no measurable decline of HPV-associated tumors before 2040. Cervical cancer alone will be diagnosed in more than 375,000 US women between now and 2040. Other HPV-associated anogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this time period. Hence, therapeutic efforts to combat high-risk HPV-associated disease remain of critical importance.

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“…No entanto, nos últimos 15 anos apenas três adjuvantes: MF59 e AS03, duas emulsões formadas pela mistura de esqualeno (C 30 H 50 ) em água (DUPUIS et al, 2001;GIUDICE, 2006) O'HAGAN; VALIANTE, 2003;CHUNG et al, 2004 flagelina, CpG DNA (DNA de origem bacteriana rico em seqüências de citosina e guanosina não metiladas), ssRNA (RNA de fita simples), dsRNA (RNA fita dupla) e imidazol-quinoline. Além disso, algumas toxinas bacterians como a toxina colérica (CT) produzida por Vibrio Cholerae, toxina termo-lábil (LT) produzida por linhagens de Escherichia coli enterotoxigênicas, a toxina pertusis (PT) produzida por Bordetella pertussis, e ainda outros produtos como o peptídeo pan HLA-DR (PADRE), específico para células T CD4 + (BARGIERI et al, , 2010, proteínas de choque térmico (hsp) (do inglês "heat shock protein"), dentre outros também exercem efeito adjuvante e estão em avaliação (GOLDSTONE et al, 2002). Mais recentemente, algumas vias de sinalização celular estão em evidência como a via de sinalização mediada por receptores intracelulares Nod-like ("Nod-like receptors") e podem representar uma nova fonte de adjuvantes quando seus mecanimos de ação forem dissecados (DE GREGORIO;TRITTO;RAPPUOLI, 2008).…”

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Pesquisa de novos adjuvantes para vacinas terapêuticas.

Braga¹

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Activity of HspE7, a Novel Immunotherapy, in Patients with Anogenital Warts

Cited by 88 publications

References 14 publications

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Human Papillomaviruses As Therapeutic Targets in Human Cancer

Pesquisa de novos adjuvantes para vacinas terapêuticas.

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