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Redirecting the Specificity of Effector Lymphocytes to Cancer and Regulatory T Cells to Inflammatory Diseases
To expand the recognition spectrum of T cells and redirect them to predefined targets, we endowed effector T and NK cells or regulatory T cells (Tregs) with antibody-type specificity using chimeric receptor genes. Several configurations employing the antibody V region cDNA in the form of scFv or ligands to target cell receptors linked to triggering subunits of the FcR or CD3 complex were constructed. Followed to the expression of these constructs in T cells, we have demonstrated their ability to trigger an MHC non-restricted or dependent T-cell upon interaction with their specific targets. In order to mediate co-stimulatory signal the cytoplasmic domains of CD28 and/or CD137 (4-1BB) were added in tandem to tripartite chimeric receptors (TPCR) and have been proven to provide a full activation and avoid activation induced cell death (AICD) of TPCR-transduced T cells independently of the presence of co-stimulatory ligands.
To expand the recognition spectrum of T cells and redirect them to predefined targets, we endowed effector T and NK cells or regulatory T cells (Tregs) with antibody-type specificity using chimeric receptor genes. Several configurations employing the antibody V region cDNA in the form of scFv or ligands to target cell receptors linked to triggering subunits of the FcR or CD3 complex were constructed. Followed to the expression of these constructs in T cells, we have demonstrated their ability to trigger an MHC non-restricted or dependent T-cell upon interaction with their specific targets. In order to mediate co-stimulatory signal the cytoplasmic domains of CD28 and/or CD137 (4-1BB) were added in tandem to tripartite chimeric receptors (TPCR) and have been proven to provide a full activation and avoid activation induced cell death (AICD) of TPCR-transduced T cells independently of the presence of co-stimulatory ligands.
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Wei-Hsin Liu,Anat Globerson Levin, Assaf Lask,Galit Horn,Tova Waks, Bar Nathansohn Levy,Maksim Mamonkin,Zelig Eshhar,Richard E. Champlin,Yair Reisner,Esther Bachar Lustig
BLOOD (2023): 4833
Anat Globerson Levin,Moran Rawet Slobodkin,Tova Waks,Galit Horn, Lihi Ninio-Many,Naamit Deshet Unger, Yaara Ohayon, Shimrit Suliman,Yael Cohen,Boris Tartakovsky,Ella Naparstek,Irit Avivi,
Cancer Research (2019): 3954-3954
G Diamant, H Simchony, T Shiloach, A Globerson-Levin,L Gasri Plotnitsky,Z Eshhar,N Pencovich,R Grossman,Z Ram,I Volovitz
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