T cell receptors that bind to NY-ESO-1 and methods of use thereof
Inventors
van Dijk, Marc • Seibert, Volker • Mundt, Cornelia Anne • Hurwitz, Arthur Andrew • Exley, Mark Adrian • Wolf, Benjamin Jacob • Leventhal, Daniel • Lalevée, Sébastien • Masakayan, Reed
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Assignees
Member
MiNK TherapeuticsMiNK Therapeutics is a clinical-stage biotechnology company focused on developing allogeneic invariant natural killer T (iNKT) cell therapies for cancer, pulmonary, and immune-mediated diseases. The company advances a platform of off-the-shelf, native and engineered iNKT cell programs capable of targeting tumors and modulating immune responses, with demonstrated clinical evidence in oncology, acute respiratory distress syndrome (ARDS), and pulmonary fibrosis. Its manufacturing platform enables large-scale GMP-compliant production and clinical delivery of iNKT cell therapies without lymphodepletion or HLA matching. MiNK collaborates with leading academic and industry partners to advance novel cell-based immunotherapies.
MiNK Therapeutics is a clinical-stage biotechnology company focused on developing allogeneic invariant natural killer T (iNKT) cell therapies for cancer, pulmonary, and immune-mediated diseases. The company advances a platform of off-the-shelf, native and engineered iNKT cell programs capable of targeting tumors and modulating immune responses, with demonstrated clinical evidence in oncology, acute respiratory distress syndrome (ARDS), and pulmonary fibrosis. Its manufacturing platform enables large-scale GMP-compliant production and clinical delivery of iNKT cell therapies without lymphodepletion or HLA matching. MiNK collaborates with leading academic and industry partners to advance novel cell-based immunotherapies.
Publication Number
US-11613764-B2
Publication Date
2023-03-28
Expiration Date
Abstract
Provided are TCRs (e.g., TCRs that bind to NY-ESO-1), cells and pharmaceutical compositions comprising these TCRs, nucleic acids encoding these TCRs, expression vectors and host cells for making these TCRs, and methods of treating a subject using these TCRs.
Core Innovation
The invention relates to an isolated TCR comprising an α chain variable region (Vα) and a β chain variable region (Vβ) with complementarity determining regions CDR1α, CDR2α, and CDR3α, and CDR1β, CDR2β, and CDR3β. The CDR amino acid sequences and variable-region sequence tables are defined by specific combinations of amino acid sequences set forth in SEQ ID NOs, including permitted α/β chain pairings and selected α-chain and β-chain amino acid sequences.
The disclosure links the defined CDRs and variable-region sequences to TCR binding to an NY-ESO-1 peptide presented in an HLA-A*0201 peptide-MHC complex. It includes exemplary NY-ESO-1-specific TCRs, peptide-MHC recognition, and functional readouts such as tetramer binding, T-cell activation markers, IFNγ secretion, and target-cell killing.
The document further describes TCR structural and functional formats, including TCRs comprising cytoplasmic and transmembrane signaling domains and co-stimulatory signaling. The disclosed TCR constructs include engineered display as soluble and/or fused constructs using furin and 2A cleavage sites, engineered mammalian and lymphocyte cells that present and express the TCR on the cell surface, and safety and effector modules including cell death and activation chimeric constructs such as FKBP12-caspase-9.
Claims Coverage
The independent claims are directed to isolated TCRs defined by specific sequence content. Two inventive features are covered: one claim defines TCR CDR amino acid sequences by enumerated SEQ ID NO combinations, and the other claim enumerates allowable α-chain and β-chain amino acid sequence selections by SEQ ID NO sets.
Isolated TCR with enumerated CDR amino-acid sequences
An isolated TCR comprising an α chain variable region (Vα) and a β chain variable region (Vβ), wherein CDR1α, CDR2α, CDR3α, CDR1β, CDR2β, and CDR3β comprise the amino acid sequences set forth in enumerated SEQ ID NO combinations.
Isolated TCR with selected α and β chain amino-acid sequences
An isolated TCR comprising an α chain and a β chain, wherein the α chain comprises an amino acid sequence selected from specified SEQ ID NO groups and the β chain comprises an amino acid sequence selected from specified SEQ ID NO groups, with further permitted α/β pairings recited in dependent claims.
The claims cover isolated TCRs defined by exact sequence identities: one claim uses CDR-defined Vα and Vβ sequence combinations, and the other uses enumerated α-chain and β-chain amino acid sequence selections and pairings.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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