Engineered platelets for targeted delivery of a therapeutic agent
AssigneeJpv01 Ltd.
InventorJames Patterson
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Abstract
The present invention provides engineered platelets with chimeric platelet receptors (CPR) with a desired target specificity. Additionally, the engineered platelets may comprise cargo which may be released upon activation of the platelet. Additionally, the platelets may be generated in vitro from megakaryocytes engineered to generate non-thrombogenic platelets.
Claims26
1-53. (canceled)
An engineered megakaryocyte or megakaryocyte progenitor cell line comprising a nucleic acid encoding a chimeric platelet receptor that recognizes and binds to a target antigen, wherein the chimeric platelet receptor comprises:
- (a) an intracellular domain of an immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor that stimulates platelet activation;
- and
- (b) an extracellular target antigen-binding domain that comprises (i) a variable heavy chain of an antibody, or an antigen-binding fragment thereof, and (ii) a variable light chain of an antibody, or an antigen-binding fragment thereof.
an engineered megakaryocyte or megakaryocyte progenitor cell line that produces platelets with reduced thrombogenic potential, comprising a disruption of or deletion of at least two genes encoding:
- (a) a protein involved in recognition of primary stimuli of thrombus formation selected from the group consisting of:
- GPIb/V/IX, GPVI (GP6), ITGA2B, CLEC2, integrins αIIbβ3, α2β1, α5β1 and/or α6β1;
- (b) a protein involved in recognition of secondary mediators of thrombus formation selected from the group consisting of Par1, Par4, P2Y12, GPIb/V/IX, the Thromboxane receptor (TBXA2R), P2Y1, P2X1 and/or integrin αIIbβ3;
- and/or
- (c) a protein involved in the release of secondary mediators of thrombus formation selected from the group consisting of Cox1, HPS and/or thromboxane-A synthase (TBXAS1).
A chimeric platelet receptor or a nucleic acid encoding the chimeric platelet receptor that comprises:
- (a) an intracellular domain of an immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor that stimulates platelet activation;
- and
- (b) an extracellular target antigen-binding domain that comprises (i) a variable heavy chain of an antibody, or an antigen-binding fragment thereof, and (ii) a variable light chain of an antibody, or an antigen-binding fragment thereof.
Dependencies are inferred from the claim text.