Luteinizing hormone receptor binding agents and luteinizing hormone agonists to identify, expand, ablate and modify stem cells
Inventors
Dudakov, Jarrod • van den Brink, Marcel • Velardi, Enrico • Kiem, Hans-Peter • Radtke, Stefan • James, Scott
Assignees
Memorial Sloan Kettering Cancer Center • Fred Hutchinson Cancer Center
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Publication Number
US-12295973-B2
Publication Date
2025-05-13
Expiration Date
Abstract
The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.
Core Innovation
The invention provides cDNA comprising a sequence as set forth in SEQ ID NO: 19 or SEQ ID NO: 6, or a sequence having at least 90% sequence identity to SEQ ID NO: 19 or SEQ ID NO: 6. The disclosed cDNA framework supports encoded components associated with an LHR binding agent and immune-therapy related constructs, including specified domain configurations and receptor/effector components.
A key aspect of the disclosure is that the cDNA can encode an LHR binding agent, and the encoded LHR binding agent is further defined using antibody-like region structures such as CDRH1, CDRH2, CDRH3, and CDRL1, CDRL2, CDRL3. The CDR composition includes specifically defined CDRL2 alternatives, and the disclosure further includes options for heavy and light chain sequence sets.
The invention further supports immune cell contexts by providing cDNA encoding immune-therapy components, including immune signaling domain and activation domains used in chimeric antigen receptor formats. The disclosed immune-therapy related constructs include combinations such as 4-1BB and CD3 zeta, and alternative embodiments include encoded CD28 hinge and CD28 transmembrane domain elements.
Claims Coverage
The independent claim defines a cDNA sequence scope using SEQ ID NO: 19 and SEQ ID NO: 6, together with at least 90% sequence identity coverage. Dependent claims then refine this core by specifying what the cDNA encodes and by constraining the encoded LHR binding agent and/or immune-therapy construct elements.
Sequence-defined cDNA with identity threshold
A cDNA comprising a sequence as set forth in SEQ ID NO: 19 or SEQ ID NO: 6 or a sequence having at least 90% sequence identity to SEQ ID NO: 19 or SEQ ID NO: 6.
cDNA encoding an LHR binding agent
The cDNA of claim 1 is specified to encode a luteinizing hormone receptor (LHR) binding agent.
cDNA encoding immune-therapy signaling and activation domains
The cDNA of claim 1 is specified to encode a 4-1BB and CD3 zeta.
cDNA encoding CD28 hinge and CD28 transmembrane domain
The claim covers a cDNA that encodes a CD28 hinge and a CD28 transmembrane domain.
cDNA encoding an LHR binding agent with defined CDR regions
The cDNA of claim 1 is specified to include CDRH1/CDRH2/CDRH3 and CDRL1/CDRL2/CDRL3 sequences defined by SEQ ID NOs, with CDRL2 having DTS, WAS, or NAS in three alternative embodiments.
cDNA located in an immune cell
The claim specifies that the cDNA of claim 1 is located within an immune cell.
Overall claim coverage is centered on a sequence-defined cDNA (SEQ ID NO: 19/SEQ ID NO: 6) with at least 90% identity coverage, and then narrows to cDNAs that encode an LHR binding agent and, in certain embodiments, immune-therapy construct components and immune-cell context, including specified domain and CDR region compositions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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