Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response

Poelgeest, Mariëtte I.E. van; Welters, Marij J.P.; Vermeij, Renee; Stynenbosch, Linda F. M.; Loof, Nikki M.; Meer, Dorien M A Berends-van der; Löwik, Margriet J.; Hamming, Ineke L. E.; Esch, Edith M.G. van; Hellebrekers, Bart W.J.; Beurden, Marc van; Schreuder, Henk W.R.; Kagie, Marjolein J.; Trimbos, J. Baptist; Fathers, Lorraine M.; Daemen, Toos; Hollema, Harry; Valentijn, A. Rob P. M.; Oostendorp, Jaap; Elberink, J Hanneke N G Oude; Fleuren, G. J.; Bosse, Tjalling; Kenter, Gemma G.; Stijnen, Theo; Nijman, Hans W.; Melief, Cornelis J.M.; Burg, Sjoerd H. van der

doi:10.1158/1078-0432.ccr-15-2594

Cited by 140 publications

(138 citation statements)

References 22 publications

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“…Indeed, as shown in two independent trials, HPV16-SLP vaccination of patients with high-grade premalignant lesions of the vulva resulted in complete regressions of the lesion in almost half of the treated patients [3,33]. Vaccination with a HPV16 E6-E7-L2 fusion protein vaccine in combination with Aldara treatment also achieved clinical success in patients with this disease [34].…”

Section: Success Of Therapy At Early Stages Of Cancer or Minimal Resimentioning

confidence: 79%

“…However, in general practice immunotherapy is applied to cancer patients with more advanced stage of disease, and as such its success is determined by the level of immunosuppression encountered in microenvironment. The treatment of premalignant lesions [3,33], but certainly that of patients with cancer, demonstrates that the increase in general and local immune suppression requires additional modalities to curtail these suppressive mechanisms and to optimally activate and expand tumor-specific T-cells. At this phase a correct sequence and interval of drugs is essential, as it will be required to use prime combinations of several modalities to obtain clinical success in the majority of patients.…”

Section: Expert Opinionmentioning

confidence: 99%

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The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

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Introduction:The treatment options for cancer-surgery, radiotherapy and chemotherapy-are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other's shortcomings. Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific Tcells but also to support and enhance their anti-tumor efficacy. Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities. ARTICLE HISTORY

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Section: Success Of Therapy At Early Stages Of Cancer or Minimal Resimentioning

confidence: 79%

Section: Expert Opinionmentioning

confidence: 99%

The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

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“…1). Cutaneous administration of imiquimod by van Poelgeest and colleagues did not increase the T-cell immune response elicited by the vaccine, but its impact on clinical response was not described (1). In murine models, peripheral vaccination with HPV16 E7 long peptides, followed by intravaginal administration of imiquimod, induced a 5-fold increase in the infiltration of vaccine-induced CD8 þ T cells in the vaginal mucosa (8).…”

Section: ó2016 Aacrmentioning

confidence: 99%

“…In this issue of Clinical Cancer Research, van Poelgeest and colleagues report the clinical results of a therapeutic human papillomavirus (HPV) vaccine for the treatment of premalignant anogenital lesions (1). Currently, two prophylactic vaccines against oncogenic HPV16 and HPV18, the genotypes predominantly found in cancers, and a new vaccine directed against 9 HPV serotypes have demonstrated their efficacy in non-HPV-infected individuals.…”

Section: ó2016 Aacrmentioning

confidence: 99%

Hope in the Long Road Toward the Development of a Therapeutic Human Papillomavirus Vaccine

Karaki

Péré

Badoual

et al. 2016

Clinical Cancer Research

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A pool of long synthetic peptides derived from HPV16 proteins induce objective partial or complete histologic regression of lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3).The intensity of T-cell response induced by the vaccine was correlated with clinical response. Clin Cancer Res; 22(10); 2317-9. Ó2016 AACR.See related article by van Poelgeest et al., p. 2342 In this issue of Clinical Cancer Research, van Poelgeest and colleagues report the clinical results of a therapeutic human papillomavirus (HPV) vaccine for the treatment of premalignant anogenital lesions (1). Currently, two prophylactic vaccines against oncogenic HPV16 and HPV18, the genotypes predominantly found in cancers, and a new vaccine directed against 9 HPV serotypes have demonstrated their efficacy in non-HPV-infected individuals. However, these vaccines failed to demonstrate any clinical activity in subjects already infected with HPV with 14 million new HPV infections each year in the world. In a subgroup of patients who do not spontaneously clear their infection, premalignant lesions will ultimately be followed by the development of invasive cancer of the cervix, anus, vagina, penis, and oropharynx. In addition, only a few countries have achieved vaccine coverage exceeding 50%. Therapeutic HPV vaccines (THV), therefore, correspond to a currently unmet medical need. van Poelgeest and colleagues report the ability of ISA 101 vaccine [13 HPV16 E6 and E7 synthetic long peptides mixed with the Montanide adjuvant] without additional treatment to induce objective partial or complete histologic regression of the lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3) with a follow-up of 12 months (1). Interestingly, 7 of 29 patients displayed complete response, which coincided with clearance of HPV16 likely to indicate complete cure. The only potential bias of this clinical trial was the absence of a control arm, but, as recalled by the authors, spontaneous regression of the lesions is observed in less than 1.5% of cases, a much lower rate than the clinical response observed after vaccination (>50%). This report therefore confirms the efficacy of ISA 101 to elicit durable complete regression in vulvar intraepithelial neoplasia (2). These results extend recent findings from a randomized control trial based on an HPV DNA vaccine, which induced regression of HPV16-or HPV18-positive CIN2/3 in 48.2% of cases compared with a spontaneous regression rate of 30% in the placebo arm (3).A different HPV DNA vaccine administered in 9 CIN3 patients also induced complete regression of lesions and viral clearance in 7 patients (4). A recombinant Modified Vaccinia Ankara (MVA) HPV16 E6 and E7 cDNA vaccine achieved cytologic clearance of CIN2/3 lesions and clearance of HPV16 virus in previously infected tissue in 7 of 10 patients (5).The first administration of THV was 1996 and, after many . Surprisingly, they did not observe a correlation be...

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“…123-128 That said, these agents technically represent antiviral vaccines and have limited activity against established HPV-driven tumors. 99,129-131 …”

Section: Introductionmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response

Cited by 140 publications

References 22 publications

The importance of correctly timing cancer immunotherapy

The importance of correctly timing cancer immunotherapy

Hope in the Long Road Toward the Development of a Therapeutic Human Papillomavirus Vaccine

Trial watch: Peptide-based vaccines in anticancer therapy

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