SBIR-STTR Award

Present pharmaceutical agents used to treat chronic, immune-mediated inflammatory diseases associated with significant morbidity and mortality generally do not lead to remission and have serious toxic side effects. This proposal offers a strategy to harness the immune system to treat systemic lupus erythematosus (SLE), a disease of generalized autoimmunity. The product will consist of the patient's own blood T cells stimulated ex-vivo to become therapeutic suppressor cells. In future clinical trials large numbers of this product will be transferred back to the patient as a medicine to ameliorate disease. Proof of concept for phase 1 studies will be to show that na ve CD4+ cells from healthy donors and subjects with SLE stimulated ex-vivo with a proprietary regulatory composition develop potent suppressive activity and protective effects. endogenous regulatory T cells. Principal developmental milestones will be to show that: 1) the product stably expresses Foxp3;2) the product has significant suppressive activity on autologous T cells both in vitro and in vivo in immunodeficient mice;3) unlike endogenous regulatory T cells, the product will be resistant to the inhibitory effects of proinflammatory cytokines;and 4) the product generated from SLE T cells suppresses both spontaneous polyclonal IgG and autoantibody production by lupus B cells. If this personalized T cell therapy is safe and successful in future clinical trials and can be produced cost effectively, this approach can become the next paradigm for not only the treatment of autoimmune diseases, but also for prevention of allograft rejection in a manner that will minimize the use of toxic anti-inflammatory or immunosuppressive agents.

Public Health Relevance:
Present pharmaceutical agents used to treat life-threatening autoimmune diseases do not generally lead to remission and have many toxic side effects. Our approach is to harness the patient's own immune system to treat systemic lupus erythematosus, one of the most severe autoimmune diseases,. Here the product will be the patient's own immune cells stimulated outside the body using a proprietary methodology to acquire the capacity to halt the progression of the disease In future clinical trials large numbers of this product will be transferred back to the patient to use as a medicine to treat the disease instead of the currently used agents.

Thesaurus Terms:
(All-E)-3,7-Dimethyl-9-(2,6,6-Trimethyl-1-Cyclohexen-1-Yl)-2,4,6,8-Nonatetraenoic Acid;7s Gamma Globulin;Atgn;Atra;Adverse Effects;After Care;After-Treatment;Aftercare;All-Trans Retinoic Acid;Anti-Dna Antibodies;Anti-Inflammatories;Anti-Inflammatory Agents;Anti-Inflammatory;Antibodies;Antibody Formation;Antibody Production;Antibody Response;Antigens;Antiinflammatories;Antiinflammatory Agents;Autoantibodies;Autoantigens;Autoimmune Diseases;Autoimmune Status;Autoimmunity;Autologous;Autologous Antigens;B Blood Cells;B Cell Differentiation Factor;B Cell Stimulating Factor 2;B-Cell Differentiation Factor;B-Cell Differentiation Factor-2;B-Cell Stimulatory Factor-2;B-Cells;B-Lymphocytes;Bcdf;Bsf-2;Bsf2;Bsf2 (B Cell Stimulating Factor 2);Back;Blood;Blood Reticuloendothelial System;Blood Serum;Bursa-Dependent Lymphocytes;Bursa-Equivalent Lymphocyte;Cd4 Cells;Cd4 Positive T Lymphocytes;Cd4 T Cells;Cd4 Lymphocyte;Cd4+ T Cell;Cd4+ T-Lymphocyte;Cd4-Positive Lymphocytes;Cd8;Cd8b;Cd8b1;Cd8b1 Gene;Cell Isolation;Cell Segregation;Cell Separation;Cell Separation Technology;Cell Therapy;Cells;Chronic;Clinical Trials;Co-Stimulator;Costimulator;Defect;Dendritic Cells;Development;Disease;Disease Progression;Disease Remission;Disorder;Dorsum;Epidermal Thymocyte Activating Factor;Epigenetic;Epigenetic Change;Epigenetic Mechanism;Epigenetic Process;Equilibrium;Equipment;Extensive Disease;Future;Generalized Disease;Generations;Goals;Hpgf;Hepatocyte-Stimulating Factor;Human;Hybridoma Growth Factor;Ifn-Beta 2;Ifnb2;Il-1;Il-2;Il-6;Il1;Il2 Protein;Il6 Protein;Igg;Immune;Immune System;Immunodeficient Mouse;Immunoglobulin G;Immunosuppressants;Immunosuppressive Agents;In Vitro;Inflammatory;Injection Of Therapeutic Agent;Injections;Interleukin 2;Interleukin 2 Precursor;Interleukin 6 (Interferon, Beta 2);Interleukin I;Interleukin Ii;Interleukin-1;Interleukin-2;Interleukin-6;Interleukine 2;Interleukine 2 Precursor;Interleukine Ii;Lyt3;Lead;Life;Lupus;Lupus Erythematosus Disseminatus;Lymphatic Tissue;Lymphocyte Mitogenic Factor;Lymphocyte-Stimulating Hormone;Lymphoid Tissue;Mgi-2;Macrophage Cell Factor;Man (Taxonomy);Mediating;Medicine;Method Loinc Axis 6;Methodology;Mice;Mice Mammals;Mitogenic Factor;Modern Man;Mononuclear;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Murine;Mus;Myeloid Differentiation-Inducing Protein;Organ System;Pbmc;Pathologic;Patients;Pb Element;Peripheral Blood Mononuclear Cell;Pharmaceutical Agent;Pharmaceuticals;Pharmacologic Substance;Pharmacological Substance;Phase I Study;Plasmacytoma Growth Factor;Prevention;Production;Regulatory T-Lymphocyte;Remission;Resistance;Retinoic Acid;Sle;Self-Antigens;Serum;Site;Specific Qualifier Value;Specified;Suppressor Cells;Suppressor-Effector T-Cells;Suppressor-Effector T-Lymphocytes;Systemic Lupus Erythematosus;Systemic Lupus Erythmatosus;Systemic Sle - Lupus Erythematosus;T Helper Factor;T Suppressor Cell;T Cell Growth Factor;T-Cell Growth Factor;T-Cell Proliferation;T-Cell Stimulating Factor;T-Cells;T-Lymphocyte;T4 Cells;T4 Lymphocytes;Testing;Therapeutic;Thymocyte Stimulating Factor;Thymus-Dependent Lymphocytes;Trans Vitamin A Acid;Treatment Side Effects;Treg;Tretinoin;Tretinoinum;Veiled Cells;Vitamin A Acid;Widespread Disease;All-Trans-Retinoic Acid;All-Trans-Vitamin A Acid;Allergic/Immunologic Body System;Allergic/Immunologic Organ System;Allograft Rejection;Antibody Biosynthesis;Autoimmune Antibody;Autoimmune Disorder;Balance;Balance Function;Base;Body System;Cell Sorting;Cell-Based Therapy;Chronic Autoimmune Disease;Clinical Investigation;Cost;Cost Effective;Cost-Effective;Cytokine;Developmental;Disease/Disorder;Disseminated Lupus Erythematosus;Fork Head Protein;Forkhead Protein;Forkhead Transcription Factors;Heavy Metal Pb;Heavy Metal Lead;Helper T Cell;Immunogen;Immunogenic;Immunoglobulin Biosynthesis;Immunosuppressive;In Vitro Assay;In Vitro Activity;In Vivo;Inhibiting Antibody;Interferon Beta 2;Lymphocyte Activating Factor;Meetings;Mouse Model;Phase 1 Study;Post Treatment;Protective Effect;Regulatory T-Cells;Resistant;Self Reactive Antibody;Self Recognition (Immune);Side Effect;Suppressor T Lymphocyte;Systemic Lupus Erythematosis;Therapy Adverse Effect;Thymus Derived Lymphocyte;Trans-Retinoic Acid;Treatment Adverse Effect