T cell receptors that bind to mixed lineage leukemia (MLL)-specific phosphopeptides and methods of use thereof
Inventors
van Dijk, Marc • Breous-Nystrom, Ekaterina Vladimirovna • FRANCHINO, Alessandra • Lalevée, Sébastien • Hurwitz, Arthur Andrew • Exley, Mark Adrian • Wolf, Benjamin Jacob
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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-12391741-B2
Publication Date
2025-08-19
Expiration Date
Abstract
Provided are TCRs (e.g., TCRs that bind to MLL, e.g., TCRs that bind to an MLL phosphopeptide, e.g., TCRs that bind to an MLL phosphopeptide/MHC complex), 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 engineered cells for treating cancer in a subject. The engineered cell comprises a T cell receptor (TCR) that includes specified CDR1α, CDR2α, CDR3α, CDR1β, CDR2β, and CDR3β amino acid sequences, as defined by SEQ ID NOs, with multiple alternative sets of CDR regions corresponding to different combinations of SEQ ID NOs.
The document describes engineered cells comprising T cell receptors that specifically bind MLL-derived phosphopeptides presented on HLA, thereby enabling T cell recognition of cancer cells. Exemplary peptide epitopes include MLL-pM (EPR[pS]PSHSM; SEQ ID NO:45) and MLL-pP (RVR[pS]PTRSP; SEQ ID NO:47), including specificity for selected phosphopeptides and variants in the context of peptide-MHC complexes, including HLA-B*0702.
The invention also relates to heat shock protein peptide complexes (HSPPCs) used together with engineered TCR/cell therapies for cancer immunotherapy. The HSPPCs include recombinant hsp70/hsc70 or gp96/heat-shock protein peptide-binding domain complexed with antigenic peptides, and an embodiment includes an autologous tumor-derived HSPPC-96 comprising gp96 complexed to antigenic peptides containing a subject-specific tumor antigen fingerprint.
The document further describes adjunct therapy options that can be used in conjunction with the engineered TCR/cell therapy and/or the HSPPC vaccine, including adjuvants such as QS-21 STIMULON, complete Freund’s adjuvant, incomplete Freund’s adjuvant, montanide ISA, and Ribi adjuvant system, as well as tumor microenvironment conditioning agents and pattern recognition receptor agonists such as TLR9 agonists and STING agonists.
Claims Coverage
The relevant independent claim coverage centers on treating cancer by administering an engineered cell expressing a TCR whose CDR1α/CDR2α/CDR3α and CDR1β/CDR2β/CDR3β amino-acid sequences are fixed to specified SEQ ID NO-defined values, with multiple alternative CDR component sets.
Engineered cell with specified TCR CDR sequences
An engineered cell comprising a T cell receptor (TCR) that includes CDR1α, CDR2α, and CDR3α amino acid sequences and CDR1β, CDR2β, and CDR3β amino acid sequences defined by SEQ ID NOs, with multiple alternative sets of those CDR components.
Treating cancer by administering the engineered cell
A method of treating cancer in a subject by administering the engineered cell expressing the specified TCR with the defined CDR amino acid sequences.
The independent claim coverage focuses on cancer treatment by administering an engineered cell with a TCR defined by specific SEQ ID NO CDR1α/CDR2α/CDR3α and CDR1β/CDR2β/CDR3β amino acid sequences, including multiple alternative CDR configurations.
Stated Advantages
T cell recognition of cancer cells.
Documented Applications
Cancer immunotherapy using engineered TCR/cell therapies together with heat shock protein peptide complexes (HSPPCs).
Use of an autologous tumor-derived HSPPC-96 vaccine comprising gp96 complexed to antigenic peptides containing a subject-specific tumor antigen fingerprint.
Assaying peptide-MHC complexes comprising MLL phosphopeptides using TCRs.
Treating MLL-expressing cancers.
Treating cancer in a subject.
Adoptive transfer tumor control in NOG mice bearing KG1a-HLA-B*0702 tumors.
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