A Phase I Clinical Trial Assessing the Safety and Immunologic Correlates of Heterologous Prime-Boost With pNGVL4a-Sig/E7(Detox)/HSP70 and TA-HPV in Healthy Donors Followed by Peripheral Blood Collection

This healthy related donor clinical trial is linked to a recipient clinical trial protocol for therapeutic purposes. In this healthy donor protocol, haploidentical relatives of a patient with recurrent or metastatic human papilloma virus (R/M HPV) 16-associated malignancy will be invited to be vaccinated with a therapeutic HPV vaccine series (PVX1) to generate HPV-specific white blood cells. In the linked recipient phase 1 clinical trial protocol, patient with incurable, locally recurrent or metastatic HPV 16-associated head and neck cancer will be randomized to one of two arms:
Arm A: non-myeloablative (NMA) allogeneic bone marrow transplant (alloBMT) OR Arm B: CD8-depleted donor lymphocyte infusion (DLI) on Day 0 of a dose escalation scheme
These two clinical trials are separated so that the healthy donor trial deals exclusively with issues of safety and immunological efficacy of the HPV vaccine series and this companion recipient trial examines the safety, feasibility and clinically efficacy of the allogeneic bone marrow graft and CD8-depleted DLI. The central hypothesis of the clinical trial is that patients with R/M HPV-associated malignancies can be safely and effectively treated by allogeneic bone marrow transplantation and/or CD8-depleted DLI from a healthy related donor that has been vaccinated against HPV16 E6 and E7 proteins.

开始日期2023-10-18

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT03911076

/ Terminated临床2期

A Randomized Double-Blind, Placebo-controlled Phase II Trial With Safety Run-In of Intramuscular pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN for the Treatment of Patients With HPV16+ Atypical Squamous Cells of Undetermined Significance (ASC-US) or Cannot Exclude High Grade SIL (ASC-H) Cytology or Low-grade Squamous Intraepithelial Lesion (LSIL)

To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6

开始日期2019-05-22

申办/合作机构

佳揚生技

[+1]

NCT00988559

/ Completed临床1期IIT

A Pilot Study of pnGVL4a-CRT/E7 (Detox) for the Treatment of Patients With HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

This study will test the efficacy and safety of different routes of administration of a DNA vaccine in patients with HPV16+ CIN2/3. Subjects will be enrolled in one of six treatment groups. Subjects enrolled in the first two groups will receive vaccination intradermally with a needle-free delivery device. Subjects enrolled in groups 3 and 4 will receive vaccination intramuscularly. Subjects enrolled in groups 5 and 6 will receive vaccine intralesionally.

开始日期2009-09-01

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

100 项与 pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN(Papivax Biotech, Inc.) 相关的临床结果

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100 项与 pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN(Papivax Biotech, Inc.) 相关的转化医学

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100 项与 pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN(Papivax Biotech, Inc.) 相关的专利（医药）

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项与 pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN(Papivax Biotech, Inc.) 相关的文献（医药）

2023-04-03·Cancer Prevention Research

Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1

Article

作者: Einstein, Mark H. ; Wu, T.C. ; Ferrall, Louise ; Chang, Yung-Nien ; Akin, Mark ; Roden, Richard B.S. ; Blomer, Allison

AbstractPatients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. The safety run-in cohort of a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein “TA-CIN”] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1 (NCT03911076) was recently completed. The primary objective of this cohort was to determine the safety and tolerability of PVX2 vaccination. Subjects were confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events were evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay was done at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage were performed at baseline and month 6. In the safety run-in cohort 12 eligible patients were enrolled. Each received three monthly immunizations. One was lost to follow-up after week 12. There were no serious adverse events. A total of five adverse events were noted by 4 patients; 4 were considered not vaccine-related, and one ‘unlikely related’ by the investigator. At month 6, 45% (5/11) of participants converted to HPV16-negative and 2 others developed CIN2+ and received a loop electrosurgical excision procedure. At month 12, 64% (7/11) were HPV16-negative, including those HPV16-negative at month 6. In conclusion, PVX2 immunotherapy was well tolerated and associated with viral regression, supporting further testing.Prevention Relevance:This safety run-in study cohort suggests that PVX2 immunotherapy is well tolerated in the target population and is sufficiently safe to warrant further clinical testing in a randomized study. The combined vaccines may facilitate higher-than-expected rate of human papillomavirus type 16 viral clearance 6 and 12 months after treatment, although this requires validation.

2018-12-01·Virology3区 · 医学

Epithelial boost enhances antigen expression by vaccinia virus for the generation of potent CD8+ T cell-mediated antitumor immunity following DNA priming vaccination

3区 · 医学

Article

作者: Ma, Ying ; Hung, Chien-Fu ; Peng, Shiwen ; Cheng, Max A ; Qiu, Jin ; Wu, T-C ; Roden, Richard B S ; Yang, Andrew ; Chang, Yung-Nien ; Farmer, Emily

While both pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV recombinant vaccinia viral vector-based vaccines have elicited HPV-specific CD8+ T cell responses in HPV16/E7-expressing tumor models, and been used as prime-boost regimen to enhance HPV-specific immune responses in humans (NCT00788164), the optimal route of administration for TA-HPV remains unclear. In a preclinical model, we examined the immunogenicity of priming with intramuscular pNGVL4a-Sig/E7(detox)/HSP70 followed by TA-HPV boost through different administration routes. We observed that priming twice with a pNGVL4a-Sig/E7(detox)/HSP70 followed by a single TA-HPV immunization boost through skin scarification generated the strongest antigen-specific CD8+ T cell response in C57BL/6 mice. These data translate to tumor control and prolonged survival of treated mice. Our results provide rationale for future clinical testing of intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine prime, TA-HPV vaccine skin scarification boost immunization regimen for the control of HPV-associated diseases.

2016-02-01·Clinical Cancer Research1区 · 医学

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

1区 · 医学

Article

作者: Sun, Yun-Yan ; Yang, Benjamin ; Peng, Shiwen ; Han, Liping ; Qiu, Jin ; Hung, Chien-Fu ; Roden, Richard B.S. ; Wu, T.-C. ; Tsai, Yachea ; Song, Liwen ; Trimble, Cornelia L.

AbstractPurpose: Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)–infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164).Experimental Design: Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc).Results: We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract.Conclusions: Our results support future clinical translation using cervicovaginal TA-HPV vaccination. Clin Cancer Res; 22(3); 657–69. ©2015 AACR.See related commentary by Nizard et al., p. 530

100 项与 pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN(Papivax Biotech, Inc.) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
HPV相关癌症	临床1期	美国	佳揚生技	2023-10-18
HPV16感染	临床1期	美国	佳揚生技	2023-10-18
肿瘤转移	临床1期	美国	佳揚生技	2023-10-18
宫颈非典型鳞状细胞	临床前	美国	佳揚生技	2019-05-22

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临床结果

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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


NCT00988559 (CTgov)	临床1期	宫颈上皮内瘤样病变	132	Gene gun vaccine+DNA vaccination (PMED Delivery - Groups 1 and 2)	繭夢憲醖築鑰鹹築簾鬱(憲鏇鏇鬱襯簾襯鑰衊顧) = 淵窪範夢壓鬱艱遞鑰壓獵願憲艱鏇夢餘築鹹醖 (壓選憲醖膚艱糧築餘衊, 糧鏇壓遞餘餘繭顧構構 ~ 積淵夢鏇醖廠觸膚鏇艱) 更多	-	2018-07-09
				therapeutic resection of the lesion+intramuscular vaccination+DNA vaccination (IM Injections - Groups 5 and 6)	繭夢憲醖築鑰鹹築簾鬱(憲鏇鏇鬱襯簾襯鑰衊顧) = 願遞簾衊鏇鹽觸醖蓋願獵願憲艱鏇夢餘築鹹醖 (壓選憲醖膚艱糧築餘衊, 窪壓鬱鏇憲膚構築膚淵 ~ 齋鏇網醖壓餘獵觸憲構) 更多