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.
Claims21
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,
- wherein the intracellular domain comprises an intracellular domain or fragment thereof from Glycoprotein VI (GPVI), C-type lectinlike receptor 2 (CLEC-2), Fc Fragment of IgG Receptor IIa (FCgR2A), high affinity immunoglobulin epsilon receptor subunit gamma (FCERG), C-Type lectin domain family 1 (CLEC1), or Fc fragment of IgG receptor II (FCGR2).
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 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,
- wherein the intracellular domain comprises an intracellular domain of any of SEQ ID NOs:
- 5, 7, 14 or 19.
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 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,
- wherein the cell line further comprises a second heterologous nucleic acid encoding a therapeutic agent that is a protein, peptide or RNA, said second heterologous nucleic acid further comprising an α-granule localization signal.
Dependencies are inferred from the claim text.