Projects & Grants
| Development of hybrid T cell receptor for targeting Fc-receptor-like 5 (FCRL5) in multiple myeloma | |
|---|---|
| Project Id | SGS15/LF/2025 |
| Main solver | Nhu Quynh Nguyen |
| Period | 1/2025 - 12/2025 |
| Provider | Specifický VŠ výzkum |
| State | solved |
| Anotation | Multiple myeloma (MM) is the second most common hematological malignancy with rising global incidence. Treatments include hematopoietic stem cell transplantation and immunotherapies like bi-specific antibodies and CAR T-cell therapy. Despite progress, CAR T-cell therapy faces challenges, such as antigen loss, leading to relapses. There is a need for new therapeutic targets and improved cell therapy strategies. Fc receptor-like 5 (FcRL5) is a surface protein selectively expressed on B and plasma cells and overexpressed in the bone marrow of MM patients. CAR T cells targeting FcRL5 show promise, but tumor escape due to low antigen expression limits their efficacy. TCR-engineered T cells mimic natural T cell activation, enabling them to target tumors with low antigen density and reducing the risk of cytokine release syndrome. However, their lower binding affinity and limited adaptability across patients remain challenges. Combining CAR and TCR technologies could overcome these limitations. This project aims to develop a hybrid TCR that integrates features of both CAR and TCR to target FcRL5. Using genome editing, we will modify the TRAC locus in human T cells to create a novel receptor structure. This hybrid receptor incorporates the immunoglobulin chains of CAR into the TCR?CD3 complex, enabling it to target cell-surface antigens with CAR-like specificity while enhancing potency against low antigen density. By merging TCR adaptability with CAR precision, this design may overcome antigen escape and improve outcomes for MM patients. |
