<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03291639</url>
  </required_header>
  <id_info>
    <org_study_id>CMUH106-REC3-107</org_study_id>
    <nct_id>NCT03291639</nct_id>
  </id_info>
  <brief_title>Functional Plasticity of Human IL-17-producing CD8+ T Cells</brief_title>
  <official_title>Functional Plasticity of Human IL-17-producing CD8+ T Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Medical University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Human Tc17 cells (IL-17-producing CD8+ T cells) have been found to contribute to different&#xD;
      kinds of human inflammatory and malignant diseases. Previous studies indicate that Tc17 cells&#xD;
      can convert to Tc1 cells (IFN-γ-producing CD8+ T cells) in tumor bearing mice to exert&#xD;
      anti-tumor effect. Base on these results in murine models, human Tc17 may have potential in&#xD;
      developing cancer immunotherapy. However, there is limited evidence to reveal the&#xD;
      characteristics and functional plasticity of human Tc17 cells. In this proposal, we aim to&#xD;
      optimize the differentiation of Tc17 cells and then investigate whether the reprograming of&#xD;
      Tc17 to Tc1 cells can promote the anti-tumor cytotoxicity. Preliminarily, we isolated CD8+ T&#xD;
      cells from the peripheral blood mononuclear cells of healthy donors to induce Tc17&#xD;
      differentiation. Human CD8+ T cells were stimulated with anti-CD3/anti-CD28 antibodies,&#xD;
      TGF-β, IL-1β, IL-6, IL-23, IL-2, anti-IFN-γ, and anti-IL-4 antibodies. After 10 days in&#xD;
      culture, there were 4% of IL-17A+IFN-γ- and 7% of IL-17A+IFN-γ+ CD8+ T cells. However, IFN-γ+&#xD;
      CD8+ T cells still represented high percentage, although it's significantly lower than that&#xD;
      in Tc1 cells. Our preliminary study demonstrated that Tc17 cells expressed lower levels of&#xD;
      cytotoxic molecules than Tc1 cells. We will further test if the expressions of cytotoxic&#xD;
      molecules, including perforin and granzyme B, and EOMES will be enhanced by various&#xD;
      cytokines. Ultimately, we will evaluate the functional plasticity of Tc17 cells under various&#xD;
      cytokine stimulation. Collectively, success of this project will establish more insight for&#xD;
      human Tc17 cells and provide the information for future developing human CD8+ T cell-mediate&#xD;
      immunotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2018</start_date>
  <completion_date type="Actual">August 30, 2018</completion_date>
  <primary_completion_date type="Actual">January 25, 2018</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Day</target_duration>
  <primary_outcome>
    <measure>Functional plasticity of IL-17+ CD8 T cells</measure>
    <time_frame>culture cells for 16 days</time_frame>
    <description>To skew human IL-17+ CD8 T cells and add specific cytokines to convert IL-17 CD8 T cells to IFN-gamma CD8 T cells</description>
  </primary_outcome>
  <enrollment type="Actual">17</enrollment>
  <condition>IL-17+ CD8 T Cells in Cancer Patients</condition>
  <eligibility>
    <study_pop>
      <textblock>
        10 healthy donors and 20 cancer patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cancer patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>July 27, 2021</last_update_submitted>
  <last_update_submitted_qc>July 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03291639
org study id: CMUH106-REC3-107
nct id: NCT03291639
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Human Tc17 cells (IL-17-producing CD8+ T cells) have been found to contribute to different
      kinds of human inflammatory and malignant diseases. Previous studies indicate that Tc17 cells
      can convert to Tc1 cells (IFN-γ-producing CD8+ T cells) in tumor bearing mice to exert
      anti-tumor effect. Base on these results in murine models, human Tc17 may have potential in
      developing cancer immunotherapy. However, there is limited evidence to reveal the
      characteristics and functional plasticity of human Tc17 cells. In this proposal, we aim to
      optimize the differentiation of Tc17 cells and then investigate whether the reprograming of
      Tc17 to Tc1 cells can promote the anti-tumor cytotoxicity. Preliminarily, we isolated CD8+ T
      cells from the peripheral blood mononuclear cells of healthy donors to induce Tc17
      differentiation. Human CD8+ T cells were stimulated with anti-CD3/anti-CD28 antibodies,
      TGF-β, IL-1β, IL-6, IL-23, IL-2, anti-IFN-γ, and anti-IL-4 antibodies. After 10 days in
      culture, there were 4% of IL-17A+IFN-γ- and 7% of IL-17A+IFN-γ+ CD8+ T cells. However, IFN-γ+
      CD8+ T cells still represented high percentage, although it's significantly lower than that
      in Tc1 cells. Our preliminary study demonstrated that Tc17 cells expressed lower levels of
      cytotoxic molecules than Tc1 cells. We will further test if the expressions of cytotoxic
      molecules, including perforin and granzyme B, and EOMES will be enhanced by various
      cytokines. Ultimately, we will evaluate the functional plasticity of Tc17 cells under various
      cytokine stimulation. Collectively, success of this project will establish more insight for
      human Tc17 cells and provide the information for future developing human CD8+ T cell-mediate
      immunotherapy.
observational model: Case-Only
time perspective: Prospective
measure: Functional plasticity of IL-17+ CD8 T cells
time frame: culture cells for 16 days
description: To skew human IL-17+ CD8 T cells and add specific cytokines to convert IL-17 CD8 T cells to IFN-gamma CD8 T cells
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Taiwan
responsible party type: Sponsor