Selective Immunotargeting of Pathogenic CD8 T Cells of Type 1 Diabetes Patients

April 22, 2014 updated by: Migal Galilee Research Institute
It is well established that CD8 and CD4 T cells reactive against defined islet antigens are associated with initiation and progression of Type 1 Diabetes (T1D). In previous work, we have demonstrated that it is possible to redirect T cells against pathogenic T cells via chimeric peptide/MHC/CD3-zeta receptors in a peptide-specific manner and to prevent, or inhibit diabetes in NOD mice. In this study we intend to extend this approach to T cells of T1D patients. Working hypothesis: Beta cell-reactive CD8 T cells of human T1D patients can be immuno-targeted by their own gene-modified cytotoxic T lymphocytes (CTLs). Aims: Our major aim is to demonstrate, in a set of ex-vivo experiments, such immunotargeting with T cells derived from T1D patients at the Ziv Medical Center. To this end we will stimulate and expand autoreactive CD8 cells in blood samples of T1D patients and target them, ex-vivo, with genetically-reprogrammed CTLs which are present in the same blood samples.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

To obtain proof-of-principle of our approach we have initiated tight collaboration between the Laboratory of Immunology at MIGAL Galilee Research Institute, Kiryat Shmona (MIGAL) and Breinin Center for Type 1 Diabetes and Endocrinology at the Ziv Medical Center in Safed (Ziv). In this study we will first identify carriers of the HLA-A0201 allele among pediatric and young adult T1D patients at Ziv. We will then screen the T cell pool in the peripheral blood samples of these patients for CD8 T cells reactive against any of 3 known HLA-A0201-binding peptides associated with autoreactivity in T1D: Insulin beta chain 10-18, IGRP 265-73 and IGRP 222-230. The influenza virus-derived peptide MP 58-66 will serve as reference. Next we will isolate polyclonal CD8 T cells from blood samples of the same patients, activate and expand them ex-vivo and transfect them via electroporation with in-vitro-transcribed mRNA encoding the respective peptide/MHC/CD3-zeta construct(s). We will then perform co-culture experiments assessing the ability of the mRNA-transfected T cells to kill the autoreactive T cells of the same patient in a peptide-selective manner.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Safed, Israel, 13100
        • Ziv Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

T1D patients who were diagnosed up to 3 years prior to recruitment

Description

Inclusion Criteria:

  • Children and young adults, ages between 0-25 who were diagnosed with T1D no more than 3 years prior to enrollment.

Exclusion Criteria:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
no treatment
T1D patients at ages 0-25
Other: blood drawing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification, isolation, propagation and targeting of autoreactive T cells from T1D patients
Time Frame: 2 years from the final approval of study
The ability of the genetically-modified cells to target and kill target autologous autoreactive CD8 T cells will be analyzed by CFSE and HLA-I tetramer staining using flow cytometry and IFN gamma production using ELISPOT.
2 years from the final approval of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Migal Galilee Research Institute

Collaborators

Ziv Medical Center

Investigators

  • Study Director: Gideon Gross, PhD, Migal Galilee Research Institute
  • Principal Investigator: Orna Gottfried, MD, Ziv Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

May 1, 2016

Study Registration Dates

First Submitted

April 16, 2014

First Submitted That Met QC Criteria

April 17, 2014

First Posted (Estimate)

April 21, 2014

Study Record Updates

Last Update Posted (Estimate)

April 23, 2014

Last Update Submitted That Met QC Criteria

April 22, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0063-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type I Diabetes

Clinical Trials on blood drawing

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe