FLT3L-Fc FUSION PROTEINS AND METHODS OF USE

Abstract

Provided are FLT3L-Fc fusion proteins, polynucleotides encoding such fusion proteins, expression cassettes, vectors, cells and kits comprising such fusion proteins, and methods of using.

1 .- 24 . (canceled) 
     
     
         25 . A fusion protein comprising: a human fins related tyrosine kinase 3 ligand (FLT3L) extracellular domain operably linked to an immunoglobulin fragment crystallizable region (Fc region), wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 14. 
     
     
         26 .- 37 . (canceled) 
     
     
         38 . The fusion protein of  claim 25 , further comprising: a second polypeptide. 
     
     
         39 .- 62 . (canceled) 
     
     
         63 . A conjugate comprising: the fusion protein of  claim 25  attached to a therapeutic agent. 
     
     
         64 .- 73 . (canceled) 
     
     
         74 . A polynucleotide encoding a fusion protein of  claim 25 . 
     
     
         75 . The polynucleotide of  claim 74 , wherein the polynucleotide is selected from the group consisting of DNA, cDNA, RNA or mRNA. 
     
     
         76 . The polynucleotide of  claim 74 , comprising a nucleic acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid sequence of SEQ ID NO: 54. 
     
     
         77 .- 93 . (canceled) 
     
     
         94 . A pharmaceutical composition comprising the fusion protein of  claim 25 , and a pharmaceutically acceptable carrier. 
     
     
         95 .- 101 . (canceled) 
     
     
         102 . A method of promoting, inducing and/or increasing the expansion and/or proliferation of a cell or a population of cells that express fins related tyrosine kinase 3 (FLT3, CD135), comprising contacting the cell or population of cells with an effective amount of the fusion protein of  claim 25 . 
     
     
         103 .- 111 . (canceled) 
     
     
         112 . A method of expanding hematopoietic stem cells (HSCs) ex vivo, comprising culturing HSCs in vitro in the presence of mesenchymal lineage precursor or stem cells (MLPSCs) and an effective amount of the fusion protein of  claim 25  such that HSCs having the phenotype CD34+ are expanded. 
     
     
         113 .- 119 . (canceled) 
     
     
         120 . A method of inducing the immune system in a subject in need thereof, comprising administering to the subject the fusion protein of  claim 25 . 
     
     
         121 . A method of preventing, reducing and/or inhibiting the recurrence, growth, proliferation, migration and/or metastasis of a cancer cell or population of cancer cells in a subject in need thereof, comprising administering to the subject an effective amount of the fusion protein of  claim 25 . 
     
     
         122 .- 123 . (canceled) 
     
     
         124 . A method of enhancing, promoting, and/or increasing the tumor infiltration of T-cells and/or NK cells in a subject in need thereof, comprising administering to the subject an effective amount of the fusion protein of any one of  claim 25 . 
     
     
         125 . A method of enhancing, promoting, and/or accelerating the recovery from or reversing the effects of lymphopenia in a subject in need thereof, comprising administering to the subject an effective amount of the fusion protein of  claim 25 . 
     
     
         126 . A method of enhancing, improving, and/or increasing the response to an anticancer therapy in a subject in need thereof, comprising co-administering to the subject (1) an effective amount of the fusion protein of  claim 25 ; and (2) an effective amount of an anticancer agent. 
     
     
         127 .- 226 . (canceled) 
     
     
         227 . A method of treating or preventing a virus infection comprising administering an effective amount of the fusion protein of  claim 25  to a subject in need thereof. 
     
     
         228 .- 231 . (canceled) 
     
     
         232 . A method of treating or preventing an HIV infection comprising administering an effective amount of the fusion protein of  claim 25 , to a subject in need thereof. 
     
     
         233 .- 237 . (canceled) 
     
     
         238 . A method of treating or preventing a human hepatitis B virus (HBV) infection comprising administering an effective amount of the fusion protein of  claim 25 , to a subject in need thereof. 
     
     
         239 .- 350 . (canceled) 
     
     
         351 . A fusion protein comprising: a human fms related tyrosine kinase 3 ligand (FLT3L) extracellular domain operably linked to an immunoglobulin fragment crystallizable region (Fc region), wherein the fusion protein comprises the amino acid sequence of any one of SEQ ID NOs: 1-13, 15-18 and 21-27. 
     
     
         352 . A polynucleotide encoding a fusion protein of  claim 351 . 
     
     
         353 . The polynucleotide of  claim 352 , comprising a nucleic acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 28-53 and 55-70.