This study has been designed to evaluate the safety and efficacy of giving seven injections of PepCan or placebo over approximately a 24-month period in subjects with head and neck cancers who achieved remission. PepCan may prove to be beneficial in treating many stages of HPV-related malignancies starting from infection to cancer. Safety, efficacy in terms of reduced cancer recurrence, immunological responses and profiles, and gut microbiome changes will be assessed.

开始日期2019-11-13

申办/合作机构

The University of Arkansas

NCT02481414 / Completed临床2期IIT

A Phase II Clinical Trial of PepCan Randomized and Double-Blinded to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions

This is a Phase II study to evaluate the efficacy and safety of a human papilloma virus (HPV) therapeutic vaccine called PepCan (HPV 16 E6 peptides combined with Candida skin testing reagent called Candin®) in adult females over a 12 month time period. As the results from the Phase I trial demonstrated some efficacy against non-16 HPV types, Candin alone will also be tested. Therefore, there will be two treatment arms: (1) PepCan and (2) Candin. Subjects found to be eligible for vaccination will be randomized in a double-blinded fashion at a 1:1 ratio. Each participant will be receiving injections four times with three weeks between injections. Clinical and virological responses will be assessed at 6 and 12 months. Safety will be assessed from the time of enrollment to 12 Month Visit. Immunological assessments will be made at 4 time points (prevaccination, after 2 injections, 6 month after 4 injections and 12 months after 4 vaccinations).

开始日期2015-11-30

申办/合作机构

The University of Arkansas

100 项与 HPV 16 E6 peptides vaccine(The University of Arkansas) 相关的临床结果

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100 项与 HPV 16 E6 peptides vaccine(The University of Arkansas) 相关的转化医学

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100 项与 HPV 16 E6 peptides vaccine(The University of Arkansas) 相关的专利（医药）

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项与 HPV 16 E6 peptides vaccine(The University of Arkansas) 相关的文献（医药）

2022-10-01·Journal for ImmunoTherapy of Cancer

Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV-16 positive (pre-)malignant lesions

Article

作者: Welters, Marij J P ; Filippov, Dmitri V ; Zom, Gijs G ; Roozen, Inge ; Krebber, Willem-Jan ; Boekestijn, Sanne ; Gelderblom, Hans ; de Vos van Steenwijk, Peggy J ; Slingerland, Marije ; Speetjens, Frank M ; Janssen, Catharina A H ; Valentijn, A Rob P M ; Melief, Cornelis J M ; Ossendorp, Ferry ; van der Marel, Gijs A ; van Poelgeest, Mariette I E ; Meeuwenoord, Nico J ; Loof, Nikki M ; van der Burg, Sjoerd H

BackgroundAmplivant is a molecularly optimized Toll-like receptor 2 ligand that can be covalently conjugated to tumor peptide antigens. In preclinical models, amplivant-adjuvanted synthetic long peptides (SLPs) strongly enhanced antigen presentation by dendritic cells, T cell priming and induction of effective antitumor responses. The current study is a first-in-human trial to investigate safety and immunogenicity of amplivant conjugated to human papillomavirus (HPV) 16-SLP.MethodsA dose escalation phase I vaccination trial was performed in 25 patients treated for HPV16 positive (pre-)malignant lesions. Amplivant was conjugated to two SLPs derived from the two most immunodominant regions of the HPV16 E6 oncoprotein. The vaccine, containing a mix of these two conjugates in watery solution without any other formulation, was injected intradermally three times with a 3-week interval in four dose groups (1, 5, 20 or 50 µg per conjugated peptide). Safety data were collected during the study. Peptide-specific T cell immune responses were determined in blood samples taken before, during and after vaccination using complementary immunological assays.ResultsToxicity after three amplivant-conjugated HPV16-SLP vaccinations was limited to grade 1 or 2, observed as predominantly mild skin inflammation at the vaccination site and sometimes mild flu-like symptoms. Adverse events varied from none in the lowest dose group to mild/moderate vaccine-related inflammation in all patients and flu-like symptoms in three out of seven patients in the highest dose group, after at least one injection. In the lowest dose group, vaccine-induced T cell responses were observed in the blood of three out of six vaccinated persons. In the highest dose group, all patients displayed a strong HPV16-specific T cell response after vaccination. These HPV16-specific T cell responses lasted until the end of the trial.ConclusionsAmplivant-conjugated SLPs can safely be used as an intradermal therapeutic vaccine to induce robust HPV16-specific T cell immunity in patients previously treated for HPV16 positive (pre-) malignancies. Increased vaccine dose was associated with a higher number of mild adverse events and with stronger systemic T cell immunity.Trial registration numbersNCT02821494and 2014-000658-12.

2019-08-01·Cancer Immunology, Immunotherapy2区 · 医学

Intratumoral delivery of an HPV vaccine elicits a broad anti-tumor immune response that translates into a potent anti-tumor effect in a preclinical murine HPV model

2区 · 医学

Article

作者: Katori, Yukio ; Chakravarty, Patrick D ; Mukhopadhyay, Anandaroop ; Ogawa, Takenori ; Wirth, Lori J ; Pai, Sara I ; Lee, Jina ; Faquin, William C ; Ishida, Eiichi ; Lin, Derrick T ; Johnson, Lauren ; Campbell, Jean S ; Pierce, Robert H

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic-polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1^hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8⁺ T cells. Overall, the CD8⁺/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs).

2011-08-01·International Journal of Cancer1区 · 医学

Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus‐associated genital tumors

1区 · 医学

Article

作者: Patrice Jichlinski ; Martine Bobst ; John T. Schiller ; Mélanie Duc ; Sonia Domingos-Pereira ; Loane Decrausaz ; Denise Nardelli-Haefliger ; Pedro Romero

AbstractCervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High‐risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene‐specific therapeutic vaccines are under development to treat HPV‐related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell‐mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE7+CD8+ and E7‐specific Interferon‐gamma‐secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long‐term protection against genital E7‐expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7‐specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein‐based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV‐associated genital cancer.

100 项与 HPV 16 E6 peptides vaccine(The University of Arkansas) 相关的药物交易

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02481414 (CTgov)	临床2期	宫颈上皮内瘤样病变 \| 鳞状上皮内病变	81	PepCan (PepCan)	艱鹹範鏇簾觸夢膚築艱(鏇餘襯鹽鬱觸鑰襯廠繭) = 鏇夢範淵膚廠構繭範願窪鹹鏇繭鏇餘選鏇鬱夢 (糧糧膚遞觸壓鹹繭製膚, 網簾壓廠襯簾蓋製鬱簾 ~ 廠簾廠簾範繭齋鹹齋製) 更多	-	2023-12-18
				Candin® (Candin)	艱鹹範鏇簾觸夢膚築艱(鏇餘襯鹽鬱觸鑰襯廠繭) = 獵繭願範遞觸積製構選窪鹹鏇繭鏇餘選鏇鬱夢 (糧糧膚遞觸壓鹹繭製膚, 築鏇膚網夢艱窪獵範選 ~ 襯獵醖鹹鏇蓋積繭廠鹽) 更多
NCT02481414 (ASCO2023) 人工标引	临床2期	宫颈上皮内瘤样病变	80	PepCan	(積積選築齋觸壓鏇衊糧) = No dose-limiting toxicity was observed 窪簾鬱顧膚醖憲夢膚夢 (範齋鏇糧醖鬱構壓艱淵 )	不佳	2023-05-31
				Candida