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Regulatory T cells (Tregs) play a key role in inducing and maintaining immune tolerance, immunosuppression, and regulating abnormal immune responses. The importance of Treg in immune regulation and intermediary tolerance has been strongly demonstrated, and expanded polyclonal Treg is being developed for clinical applications. However, one problem is that the frequency of specific Tregs is very low. To overcome this issue, Creative Biolabs strive to "designate" Tregs by engineering Tregs to express receptors that recognize a given antigen. Therefore, we use retroviruses to transduce specific T-cell receptors, single-chain variable fragments (Fvs), or antigen domains to achieve this goal, and this scheme is promising for autoimmunity, hemophilia, and allergy.
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Specific Treg 1: TCR- Tregs T cell receptors (TCR) can recognize tumor-specific proteins inside cells. When tumor-specific proteins break down into fragments, they will appear on the cell surface along with another protein called the major histocompatibility complex (MHC). TCR is designed to recognize tumor-specific protein fragments / MHC combination1. Here, we cloned HLA-restricted TCR derived from hemophilia patients, constructed a TCR-retroviral recombinant vector, and then transduced human Treg. These TCR-transduced Tregs show robust bystander effect for suppression. |
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Specific Treg 2: CAR- Tregs Although TCR transduced Tregs are very effective, they are still restricted by MHC class II. Therefore, we developed a second engineering-specific method, scFv, just like chimeric antigen receptor (CAR) T cells for cancer treatment. The scFv that recognizes specific antigens is integrated into our retroviral CAR vector for transduction of Treg. These scFv CAR Tregs can inhibit antibody responses against multiple epitopes in specific antigens. These data provide evidence that engineering Tregs suppress bystanders. |
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Specific Treg 3: Antigen- Tregs We have developed another Treg that expresses homologous antigens recognized by B cells through their IgM and IgD receptors and can directly target B cells. The antigen protein that recognizes specific B cell antibody receptor is integrated into our retroviral CAR vector for transduction of Treg. The data shows that when specific B cells encounter engineered antigen-Treg cells, they will bind to Treg and form synapses, and will receive a putative negative signal from these Tregs cells, resulting in the suppression of B cell response or cell death. |
One-stop Engineered Treg Therapy Development
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