Multi-receptor natural killer cells
AssigneeBoard of Regents, The University of Texas System
InventorsKaty REZVANI, Rafet BASAR, Nadima UPRETY, Bin LIU
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Abstract
Embodiments of the disclosure include methods and compositions in which NK cells are modified by the hand of man to express a heterologous a) polypeptide comprising a CD16 Fc binding domain, b) a T Cell Receptor (TCR, e.g., an invariant T Cell Receptor (iTCR)), and c) a CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with monospecific, bispecific, and/or multi-specific antibodies, that may have modified or non-modified Fc domains.
Claims140
An engineered immune cell comprising, one or more transgenic polynucleotides encoding:
- a) a CD3 protein complex comprising part or all of a single chain or any combination of CD3ζ, CD3δ, CD3ε, or CD3γ,
- b) optionally at least one cytokine,
- c) at least one TCRβ and TCRα chain and/or a TCRγ and TCRδ chain, and
- d) a polypeptide comprising a CD16 Fc binding domain.
A kit comprising the immune cell, composition, means for performing the method, and/or polynucleotide of any one of the preceding claims, and one or more antibodies.
Use of the immune cell, composition, kit, and/or polynucleotide of any one of the preceding claims for medicinal and/or biomedical research purposes.
A method of treating a disease or disorder in an individual, the method comprising administering to the individual an engineered NK cell and one or more antibodies, wherein the engineered NK cell comprises one or more transgenic polynucleotides with coding sequences that are:
- a) at least about 80%, 85%, 90%, 95%, 98%, or 100% identical to any one or more of SEQ ID NOs:
- 172, 171, 173, 174, or 175, and
- b) at least about 80%, 85%, 90%, 95%, 98%, or 100% identical to any one or more of SEQ ID NOs:
- 48, 46, or 50.
A polynucleotide comprising a sequence at least about 80%, 85%, 90%, 95%, 98%, or 100% identical to any one of transcriptional reading frames represented by SEQ ID NOs:
- 172, 171, 173, 174, or 175.
A polynucleotide comprising a sequence encoding a T cell receptor (TCR) beta and a TCR alpha polypeptide, and/or TCR gamma and TCR delta polypeptide, and a polypeptide comprising a CD16 derived Fc binding domain.
Dependencies are inferred from the claim text.