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

NCT02117518 | Unknown

• 1 other identifier: 0063-13
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type I Diabetes

Keywords

type 1 diabetes; autoreactive T cells; beta cell peptides; genetically modified T cells; mRNA electroporation

Outcome Measures

Primary Outcomes (1)

• Identification, isolation, propagation and targeting of autoreactive T cells from T1D patients

  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

Study Arms (1)

no treatment

T1D patients at ages 0-25

Other: blood drawing

Interventions

blood drawing OTHER

no treatment

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• none

Sponsors & Collaborators

• Migal Galilee Research Institute: lead
• Ziv Medical Center: collaborator

Study Sites (1)

Ziv Medical Center

Safed, 13100, Israel

Location

Biospecimen

Retention: NONE RETAINED

Blood samples

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gideon Gross, PhD

  Migal Galilee Research Institute

  STUDY DIRECTOR

• Orna Gottfried, MD

  Ziv Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 21, 2014
• Study Start: May 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

IL (1)