Primary Organoid Models and Combined Nucleic Acids Therapeutics for Anti-HPV Treatments

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Brief Title

Primary Organoid Models and Combined Nucleic Acids Therapeutics for Anti-HPV Treatments

Official Title

Primary Organoid Models and Combined Nucleic Acids Therapeutics for Innovative Anti-HPV Treatments in Cervico-vaginal Cancers and Precancerous Lesions

Brief Summary

      Human papilloma virus (HPV) is responsible of the most common sexually transmitted infection.
      It can cause severe cancer lesions, of the cervix, vulva, vagina, penis and oropharynx. The
      International Agency for Cancer Research of World Health Organization (WHO) classified a
      dozen of HPV related high-risk cancer types, and recognized cervical cancer as the most
      common HPV-related disease. HPV 16 and 18 are responsible for 70% of cervical cancers.

      Due to the few symptoms of cervical cancer, women are often diagnosed with advanced state.
      Current treatments imply cervical conisation or hysterectomy, with or without lymphadenectomy
      and or radiotherapy, or chemotherapy.

      However, few pharmacological options are available against oncogenic papilloma viruses and
      thus against recurrences The aim of this project is to develop relevant organoids models from
      patient biopsies that will be used to identify biomarkers and evaluate in a closest
      preclinical setting novel nucleic acids based therapeutic strategy for HPV-cervical-vaginal
      dysplasia and cancers.
    

Detailed Description

      In this project, the investigators want to develop organotypic culture of primary-derived
      biopsies, and combine them with organ-on-a-chip technology, to better characterize the HPV
      infection and cancer progression, as well as to screen innovative treatments for cervical and
      vaginal cancers.

      Our study will cover cervical dysplasia and cervical cancers HPV induced. The investigators
      will perform cervical and or vaginal biopsies from patients with oncogenic HPV lesions. A
      protocol validated to collect biopsies from precancerous cervico-vaginal lesions or cervical
      cancer patients in CHRO (Orleans, France). The biopsies will be performed during a
      consultation in the Hospital center of Orleans, or in the theatre room during a conisation or
      an hysterectomy. The PRIMMO platform is the research platform of Regional hospital center of
      Orleans (CHRO) dedicated to the promotion of translational research. It will be involved in
      the collection, analysis and biobank storage setup of the project. Fresh samples will be
      collected and bring directly to the lab for organoid cell culture development. Detection of
      HPV in each biopsy will be carried out by the PRIMMO platform.

      The organoid development from patient biopsies will take place into the lab of the Biophysic
      Molecular center in Orleans.

      The organoids will be selected according to three criteria: their ability to grow until a
      first passage, their doubling time and their ability to be frozen and resuscitated. Such
      organoids maintain pathogen-host interaction and better model physiopathology of vaginal
      cervical dysplasia CIN2-3 or cervical cancer and thus allow for the detection of biomarkers
      for pre-cancerous lesions. In addition, organoids reduce the use of animal models and can be
      used for drug screening, In a second step, the investigators propose to use mRNA to produce
      in situ the nanobodies targeting E6 and E7, to inhibit viral replication and tumor growth

      Socio-epidemiological data will be collected for each patient, in the form of a table.

      The study could be stopped in case of serious undesirable events. Safety evaluation As this
      is a category 2 study, no particular vigilance linked to the research protocol will be
      useful.

      However, the monitoring and reporting of unexpected events resulting from participation in
      the study will be declared to the "materiovigilance site" of the CHR of Orleans Given the
      minimal risks associated with the study, an independent monitoring committee was not
      considered necessary.
    


Study Type

Interventional


Primary Outcome

To develop a 3D vaginal organoid culture model.

Secondary Outcome

 Inhibition of HPV molecular therapeutics using oligonucleotide, and siRNA (small interfering RNA)

Condition

HPV Infection

Intervention

Vaginal Biopsy

Study Arms / Comparison Groups

 Experimental
Description:  Patients infected by oncogenic HPV and presented a high grade cervical dysplasia or a cervical cancer
Patients with cervical or vaginal cancer
All patients

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

50

Start Date

March 6, 2020

Completion Date

April 2024

Primary Completion Date

April 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Patients between 18 and 75 years old.

          -  Patients presented with cervical or vaginal dysplasia or cancer induced by oncogenic
             HPV demonstrated by a PAP test and or HPV testing requiring a biopsy and histology in
             current care.

        Patients with previous history of conisation or hysterectomy for lesions of the cervix or
        the vagina caused by oncogenic HPV.

        To participate in the study, patients must sign an informed consent.

        Exclusion Criteria:

          -  - Pregnant women

          -  Patients with coagulation disorders

          -  Refusal of patients to participate in the trial Patients not affiliated to medical
             insurance

          -  Person deprived of their liberty by judicial or administrative decision

          -  Adults over 18 who are under legal protection measures or cannot give their consent
      

Gender

Female

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Souhail ALOUINI, M.D.,Ph.D., +33238744071, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04278326

Organization ID

CHRO-2019-08


Responsible Party

Sponsor

Study Sponsor

Centre Hospitalier Régional d'Orléans

Collaborators

 CNRS - Pr Chantal PICHON

Study Sponsor

Souhail ALOUINI, M.D.,Ph.D., Principal Investigator, CHR Orléans


Verification Date

April 2021