CPC A61K 39/3955 (2013.01) [A61K 9/0019 (2013.01); A61K 9/127 (2013.01); A61K 9/51 (2013.01); A61K 38/177 (2013.01); A61K 38/1774 (2013.01); A61K 48/005 (2013.01); A61P 35/00 (2018.01); C07K 2317/622 (2013.01); C07K 2319/00 (2013.01)] | 20 Claims |
1. 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-TROP2 binding domain, and
(b) a transmembrane domain operatively linked to the extracellular domain;
wherein the transmembrane domain is a transmembrane domain from a protein that dimerizes with endogenous FcR-gamma receptors expressed in myeloid cells, monocytes or macrophages of the subject;
wherein the CFP is expressed on the surface of myeloid cells that express endogenous FcR-gamma receptors wherein the anti-TROP2 binding domain comprises a Fab fragment or an scFv domain comprising a heavy chain variable domain and a light chain variable domain on a single polypeptide chain linked via a linker;
and wherein the anti-TROP2 binding domain comprises
(a) a heavy chain complementarity determining region 1 (HC CDR1), a HC CDR2 and a HC CDR3 of SEQ ID NO: 34, and a light chain complementarity determining region 1 (LC CDR1), a LC CDR2 and a LC CDR3 of SEQ ID NO: 34; or
(b) a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO: 35, and a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 35.
|