Delving into the Latest Updates on GTL-001 with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Therapeutic vaccine

Synonyms

CyAa-HPV-16E7 CyaA-HPV-18E7 vaccine, HPV 16E7 HPV 18E7 protein vaccine, ProCervix

+ [3]

Target-

Action

stimulants

Mechanism

CD4-positive T-lymphocytes stimulants, CD8-positive T-Lymphocytes stimulants

Therapeutic Areas

NeoplasmsInfectious DiseasesUrogenital Diseases+ [1]

Active Indication-

Inactive Indication

Atypical Squamous Cells of the CervixGenital infectionHPV16 Infection+ [2]

Originator Organization

Genticel SA

Active Organization-

Inactive Organization

Genticel SA

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Human Papillomavirus (HPV) 16 and HPV 18 (the two virus genotypes targeted by the ProCervix vaccine) are the most common HPV genotypes associated with at least 70% of squamous cell carcinomas and 82% of adenocarcinomas of the cervix The strategy of therapeutic vaccination with ProCervix is to activate and enhance the patient's cellular immune response to HPV . The therapeutic vaccine will be used for women infected by HPV 16, HPV 18, or both. The vaccine targets these HPV infected women with normal or mild cervical cellular dyskaryosis as detectable infections with oncogenic potential.
This will be a double-blind, randomised, placebo-controlled, parallel group study assessing the efficacy of ProCervix or placebo (concomitantly administered with imiquimod cream).
ProCervix will be delivered with a topical agent, imiquimod, applied to the injection sites as a vaccine adjuvant.
The population proposed for this study represents an otherwise healthy female population who are infected with HPV 16 and/or HPV 18. The safety and tolerability of this therapeutic vaccine has been shown in the ongoing Phase I study, and the proposed population may in theory derive benefit from this vaccine.

Start Date01 Dec 2013

Sponsor / Collaborator

Genticel SA

NL-OMON35990

/ CompletedNot Applicable

Tolerance and immunogenicity of ProCervix, a therapeutic vaccine composed of 2 Human Papillomavirus (HPV) antigens vectored in recombinant adenylate cyclases, in HPV 16 and/or HPV 18 infected women with normal cytology - Tolerance and immunogenicity of ProCervix, a HPV-16 /18 therapeutic vaccine

Start Date12 Jan 2012

Sponsor / Collaborator-

100 Clinical Results associated with GTL-001

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100 Translational Medicine associated with GTL-001

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100 Patents (Medical) associated with GTL-001

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6

Literatures (Medical) associated with GTL-001

12 Jun 2023·Laboratory animal research

Development of HPV16 mouse and dog models for more accurate prediction of human vaccine efficacy.

Article

Author: Martin, Nicolas ; Pavlovic, Guillaume ; Misseri, Yolande ; Bousquet-Melou, Alain ; Boullier, Severine ; Sorg, Tania ; Iché, Alexandra ; Lindner, Loïc ; Totain, Emmanuelle ; Duthoit, Christine ; Herault, Yann ; Bouillé, Pascale ; Birling, Marie-Christine

BACKGROUNDAnimal models are essential to understand the physiopathology of human diseases but also to evaluate new therapies. However, for several diseases there is no appropriate animal model, which complicates the development of effective therapies. HPV infections, responsible for carcinoma cancers, are among these. So far, the lack of relevant animal models has hampered the development of therapeutic vaccines. In this study, we used a candidate therapeutic vaccine named C216, similar to the ProCervix candidate therapeutic vaccine, to validate new mouse and dog HPV preclinical models. ProCervix has shown promising results with classical subcutaneous murine TC-1 cell tumor isografts but has failed in a phase II study.RESULTSWe first generated E7/HPV16 syngeneic transgenic mice in which the expression of the E7 antigen could be switched on through the use of Cre-lox recombination. Non-integrative LentiFlash^® viral particles were used to locally deliver Cre mRNA, resulting in E7/HPV16 expression and GFP reporter fluorescence. The expression of E7/HPV16 was monitored by in vivo fluorescence using Cellvizio imaging and by local mRNA expression quantification. In the experimental conditions used, we observed no differences in E7 expression between C216 vaccinated and control groups. To mimic the MHC diversity of humans, E7/HPV16 transgenes were locally delivered by injection of lentiviral particles in the muscle of dogs. Vaccination with C216, tested with two different adjuvants, induced a strong immune response in dogs. However, we detected no relationship between the level of cellular response against E7/HPV16 and the elimination of E7-expressing cells, either by fluorescence or by RT-ddPCR analysis.CONCLUSIONSIn this study, we have developed two animal models, with a genetic design that is easily transposable to different antigens, to validate the efficacy of candidate vaccines. Our results indicate that, despite being immunogenic, the C216 candidate vaccine did not induce a sufficiently strong immune response to eliminate infected cells. Our results are in line with the failure of the ProCervix vaccine that was observed at the end of the phase II clinical trial, reinforcing the relevance of appropriate animal models.

01 Mar 2017·VaccineQ3 · MEDICINE

GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory T-cell responses that inhibit tumor growth

Q3 · MEDICINE

Article

Author: Leung-Theung-Long, Stéphane ; Bissery, Marie-Christine ; Goubier, Anne ; Esquerré, Michaël ; Momot, Marie ; Gonindard, Christophe ; Misseri, Yolande

GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8⁺ T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8⁺ T-cell responses to both vaccine antigens. Intradermal vaccination of C57BL/6 mice with GTL001 adjuvanted with a TLR3 agonist (polyinosinic-polycytidylic acid) or a TLR7 agonist (topical 5% imiquimod cream) induced strong HPV16 E7-specific T-cell responses capable of eradicating HPV16 E7-expressing tumors. Tumor-free mice also had antigen-specific memory T-cell responses that protected them against a subsequent challenge with HPV18 E7-expressing tumor cells. In addition, vaccination with bivalent vaccines containing CyaA-HPV16 E7 and CyaA fused to a tumor-associated antigen (melanoma-specific antigen A3, MAGEA3) or to a non-viral, non-tumor antigen (ovalbumin) eradicated HPV16 E7-expressing tumors and protected against a later challenge with MAGEA3- and ovalbumin-expressing tumor cells, respectively. These results show that CyaA-based bivalent vaccines such as GTL001 can induce both therapeutic and prophylactic anti-tumor T-cell responses. The CyaA platform can be adapted to different antigens and adjuvants, and therefore may be useful for developing other therapeutic vaccines.

01 Jul 2016·Clinical Cancer ResearchQ1 · MEDICINE

GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Q1 · MEDICINE

Article

Author: Timmerman, Benedikt ; Depuydt, Christophe ; Hens, Annick ; Bissery, Marie-Christine ; Hercend, Thierry ; Cools, Nathalie ; Goubier, Anne ; Van Damme, Pierre ; De Coster, Ilse ; Bouillette-Marussig, Myriam ; Van Tendeloo, Viggo ; Goossens, Herman

AbstractPurpose: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if high-grade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology.Experimental Design: This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 μg GTL001 + topical 5% imiquimod cream at the injection site. In a double-blind part, subjects were randomized 2:1:1 to two vaccinations 6 weeks apart of 600 μg GTL001 + imiquimod, 600 μg GTL001 + placebo cream, or placebo + imiquimod.Results: Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 μg GTL001 + imiquimod group. In post hoc analyses, the 600 μg GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigen-specific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA.Conclusions: For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. Clin Cancer Res; 22(13); 3238–48. ©2016 AACR.

100 Deals associated with GTL-001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Atypical Squamous Cells of the Cervix	Phase 2	France	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	United Kingdom	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Belgium	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Finland	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	France	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Belgium	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Finland	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	United Kingdom	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Spain	Genticel SA	01 Dec 2013
Atypical Squamous Cells of the Cervix	Phase 2	Spain	Genticel SA	01 Dec 2013