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CellRapeutics™ TCR/CAR/Antigen-Engineered Regulatory T Cells (Tregs)

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.

CellRapeutics™ TCR/CAR/Antigen-Engineered Regulatory T Cells (Tregs)

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.

CellRapeutics™ TCR/CAR/Antigen-Engineered Regulatory T Cells (Tregs)

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.

CellRapeutics™ TCR/CAR/Antigen-Engineered Regulatory T Cells (Tregs)

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

Biomarker Identification & Selection Biomarker Identification & Selection
CAR/TCR Design & Construction CAR/TCR Design & Construction
Virus Packaging & Gene Delivery Virus Packaging & Gene Delivery
In Vitro Assay In Vitro Assay
Preclinical In Vivo Assay Preclinical In Vivo Assay
Clinical Trial Clinical Trial

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Scott, D. W. (2019). Genetic engineering of T cells for immune tolerance. Molecular Therapy-Methods & Clinical Development.

All services and products are only for lab research use, not for any clinical diagnosis or treatment.

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