A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families.
Jie WangKatarzyna UrbanskaPrannda SharmaReza NejatiLauren ShawMegan S LimStephen J SchusterDaniel J Powell JrPublished in: Vaccines (2020)
Peripheral T cell lymphomas (PTCLs) are generally chemotherapy resistant and have a poor prognosis. The lack of targeted immunotherapeutic approaches for T cell malignancies results in part from potential risks associated with targeting broadly expressed T cell markers, namely T cell depletion and clinically significant immune compromise. The knowledge that the T cell receptor (TCR) β chain in human α/β TCRs are grouped into Vβ families that can each be targeted by a monoclonal antibody can therefore be exploited for therapeutic purposes. Here, we develop a flexible approach for targeting TCR Vβ families by engineering T cells to express a chimeric CD64 protein that acts as a high affinity immune receptor (IR). We found that CD64 IR-modified T cells can be redirected with precision to T cell targets expressing selected Vβ families by combining CD64 IR-modified T cells with a monoclonal antibody directed toward a specific TCR Vβ family in vitro and in vivo. These findings provide proof of concept that TCR Vβ-family-specific T cell lysis can be achieved using this novel combination cell-antibody platform and illuminates a path toward high precision targeting of T cell malignancies without substantial immune compromise.
Keyphrases
- monoclonal antibody
- cancer therapy
- poor prognosis
- regulatory t cells
- long non coding rna
- cell therapy
- drug delivery
- healthcare
- endothelial cells
- binding protein
- human health
- high throughput
- squamous cell carcinoma
- radiation therapy
- nk cells
- dendritic cells
- mesenchymal stem cells
- climate change
- bone marrow
- small molecule
- locally advanced
- chemotherapy induced
- amino acid
- replacement therapy