Engineered chimeric fusion protein compositions and methods of use thereof

A method of treating a GPC3-expressing cancer in a subject in need thereof, comprising:

• administering to the subject a therapeutically effective amount of a composition comprising a recombinant polynucleic acid encapsulated by a nanoparticle delivery vehicle, wherein the recombinant polynucleic acid comprises a sequence encoding a chimeric fusion protein (CFP), the CFP comprising:
• (a) an extracellular domain comprising an anti-GPC3 binding domain, wherein the extracellular domain further comprises an extracellular domain or fragment thereof from CD16a, CD64, CD68 or CD89, and
• (b) a transmembrane domain operatively linked to the extracellular domain, wherein the transmembrane domain comprises a transmembrane domain from CD16a, CD64, CD68 or CD89;
• wherein the CFP is expressed on the surface of myeloid cells of the subject that express endogenous FcR-gamma receptors;
• wherein the anti-GPC3 binding domain comprises:
• (i) a heavy chain comprising a heavy chain variable domain, the heavy chain variable domain comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence of DYEMH (amino acid residues 31-35 of SEQ ID NO:
• 97), a HC CDR2 sequence of ALDPKTGDTAYSQKFKG (amino acid residues 50-66 of SEQ ID NO:
• 97) and a HC CDR3 (HC CDR3) sequence of FYSYTY (amino acid residues 99-104 of SEQ ID NO:
• 97);
• and
• (ii) a light chain comprising a light chain variable domain comprising:
• a light chain complementarity determining region 1 (LC CDR1) sequence of RSSQSLVHSNRNTYLH (amino acid residues 24-39 of SEQ ID NO:
• 98), a LC CDR2 sequence of KVSNRFS (amino acid residues 55-61 of SEQ ID NO:
• 98) and a LC CDR3 sequence of SQNTHVPPT (amino acid residues 94-102 of SEQ ID NO:
• 98).