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OwnerJürgen Herbert Ernst Kuball, Victoria Marcuinventors
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The current invention provides methods to identify γ9δ2T-cell receptors (γ9δ2TCR) that mediate anti-tumour responses. Surprisingly, it was now found that the CDR3 regions of the γ9-T-cell receptor chain and the δ2-T-Cell receptor chain (δ2TCR chain) are of importance. Based on these findings, combinatorial-γδTCR-chain-exchange (CTE) is proposed as an efficient method for identifying γ9δ2TCRs that mediate anti-tumour responses. Using the method of the invention, specific sequences of the respective γ9TCR and δ2TCR chains were identified that mediate anti-tumour responses. Hence, the invention further provides for specific γ9δ2TCRs, or fragments thereof, that may be used e.g. in diagnostics or treatment of cancer. The invention further provides for nucleic acid sequences, genetic constructs and retroviral vectors that can be used to express the γ9δ2TCRs according to the invention.
A composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor, wherein the exogenous γ9δ2T-cell receptor comprises a γ9T-cell receptor comprising an amino acid sequence at least 95% identical to amino acid residues 21-315 of SEQ ID NO:
A composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor, wherein the exogenous γ9δ2T-cell receptor comprises a γ9-CDR3 region with an amino acid sequence at least 60% identical to residues 118-132 of SEQ ID NO. 1 and a δ2-CDR3 region comprising an amino acid sequence at least 60% identical to residues 112-127 of SEQ ID NO. 2.
A composition comprising an engineered αβ T-cell that expresses an exogenous γ9δ2T-cell receptor, wherein the exogenous γ9δ2T-cell receptor comprises a γ9-CDR3 region with an amino acid sequence at least 85% identical to SEQ ID NO. 16 and a 62-CDR3 region comprising an amino acid sequence at least 85% identical to SEQ ID NO. 17.
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