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Induced Tolerogenic Dendritic Cells as Modulators of Allergic Asthma (MGH-002)
Despite advances in medications, allergic diseases, including allergic asthma continue to rise in prevalence. For this reason, there is a need for a better understanding of the mechanisms of allergic diseases and novel insights into modulating allergic inflammation. The investigators hypothesize that much remains to be learned about the behavior of T effector and T regulatory cells in allergic disease. Furthermore, the investigators hypothesize that novel mechanisms of allergic tolerance may exist, and elucidation of these mechanisms may provide insights into novel therapeutic strategies to control allergic diseases. The investigators will investigate the capacity for T cell tolerance induction in allergic subjects by a novel type of immune tolerizing dendritic cell (it-DC). The investigators will assess whether in vitro generated it-DCs have the capacity to induce antigen-specific T regulatory cells and suppress allergen-specific T effector cell function in vitro. Standardized Cat Allergen extract and Dust Mite Allergens will be used to generate changes in the airways that occur during exposure to allergen. For this investigation, the route of administration will be topical application of the titrated allergen to a bronchoscopically isolated subsegment of one lobe of one lung. The dose of biologic will be determined from prior skin-prick testing.
Details
| Lead sponsor | Andrew D. Luster, M.D.,Ph.D. |
|---|---|
| Phase | Phase 1 |
| Status | COMPLETED |
| Enrolment | 43 |
| Start date | 2013-01 |
| Completion | 2016-09 |
Conditions
- Asthma
- Allergies
Interventions
- Bronchoscopy, Segmental Allergen Challenge and Bronchoalveolar Lavage
- Phlebotomy
Primary outcomes
- Effect of it-DC on the phenotype, function, proliferation and survival of allergen-specific effector T cells. — 24 hours
We will generate induced tolerogenic dendritic cells (it-DCs) in vitro from peripheral blood monocytes and dendritic cells isolated from each allergic asthmatic subject and assess their capacity to (a) attenuate effector CD4+ T cell (Teff) responses and/or (b) induce T regulatory (Treg) cells from Teff cells as well as CD4+ naïve and memory T cells. Attenuation of T cell responses (a) will be assessed by proliferation assays and cytokine production. Moreover, in order to evaluate the functionality of the it-DC induced Tregs (b), co-culture suppression assays using cat or house dust-mite allergen-specific Teff cells isolated from BAL following segmental allergen challenge (SAC) as responder cells, will be examined. The percent suppression of responding Teff cells will be assessed by examining Teff cell proliferation and survival/apoptosis, and by cytokine production. (Note: SAC samples from healthy controls are not involved in the primary analysis.)
Countries
United States