Autologous EBV-specific Cytotoxic T Cells for the Treatment of Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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EBV has been implicated in pathogeny of SLE with increase in EBV sero-prevalence, defective control in EBV infection and altered both B and T immune responses to this virus The main objective of this pilot proof-of-concept (POC) study is to evaluate safety and efficacy of autologous EBV specific CTL adoptive transfer in adult patients with serologically active SLE

Detailed Description
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Systemic lupus is a disabling disease of the young woman, whose treatment is based on the long-term corticosteroid, anti-malarials and immunosuppressants synthesis. This support is not without potential side effects. EBV is a herpes causes infectious mononucleosis virus, usually encounter in childhood or adolescence, and that our natural immunity cell (CD8 T cells) controls all our lives, not eliminate. Increasingly scientific studies show that there are patients with systemic lupus (and multiple sclerosis), a failure of self-control of the EBV virus, by T lymphocytes (CD8). This uncontrolled virus then stimulate the B lymphocytes, which produce antibodies, toxic in lupus. The laboratory isolate T cells specific for EBV (EBV-CTL) of a patient, and stimulate in culture to strengthen them. They can be then re-injected by a single intravenous infusion (autotransfusion), and were used to control the virus in certain diseases where EBV has a demonstrated role post-transplant lymphoproliferative disorder, chronic fatigue syndrome EBV-induced. Our therapeutic approach is completely innovative, as based on the principle of cell therapy, thus not using new drugs, and based on the restoration of the patient's immune system, specific EBV.

Official Title
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Restauration of EBV Control in SLE Phase 1-2 Trial Evaluating Adoptive Transfer of Autologous EBV- Specific Cytotoxic T Lymphocytes in SLE Treatment

Conditions
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Serologically Active Adult Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Autologous EBV specific CTL infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 4 systemic lupus criteria of the American College of Rheumatology with antinuclear antibodies> 1:80 Age greater than or equal to 18 years Lupus serologically active without active serious disease (Kidney, CNS) Anti-native DNA Ac positive and / or C3 or C4 low SLEDAI greater than or equal to 2 at baseline Serology HBV, HCV, HIV, HTLV-1, syphilis: Negative J-30 before sample Hemoglobin >11g/dL Prednisone dose <15 mg / day with a stable dose within 30 days previous injection Immunosuppressive treatments which dosage has not been increased for at least 3 months before enrollment Agreement telephone and / or mail for coordinating investigator inclusion Social ensured Patient EBV positive serology Exclusion Criteria: Evolving severe lupus, requiring high dose corticosteroids and / or immunosuppressive therapy Psychiatric disorders Predicted Failure to monitoring compliance with impossibility Infectious Episode underway Evolutionary Cancer Risk of death within 6 months Consent Refusal Pregnancy Nursing women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous EBV specific CTL infusion<br> | Biological: Autologous EBV specific CTL infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| description of adverse events according CTC toxicity criteria . | Tolerance will be assessed by clinical and laboratory examinations to each Visit according to CTC toxicity criteria. | month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Lupus Erythematosus clinical activity | Composite Response of SLE Index (Systemic Lupus Erythematosus Responder Index: Systemic Lupus Erythematosus Disease Activity Index + British Isles Lupus Assessment Group + Physician Global Assessment) | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Quality of Life, The Short Form (36) Health Survey | The Short Form (36) Health Survey | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Lupus Quality of Life | Lupus Quality of Life questionnaire | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Systemic Lupus Erythematosus biological activity (1) | biological parameter measurement biomarkers C3 | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Systemic Lupus Erythematosus biological activity (2) | biological parameter measurement biomarkers C4 | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Systemic Lupus Erythematosus biological activity (3) | biological parameter measurement biomarkers anti-dsDNA antibodies | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 
| Systemic Lupus Erythematosus biological activity (4) | biological parameter EBV blood load | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic lupus erythematosus, autologous anti-EBV CTL, adoptive therapy, phase 1 -2