Nanoparticles Having Molecules That Bind or Block PD-L1 and Uses In Treating Cancer

Abstract

This disclosure relates to nanoparticles comprising a surface molecule that binds or blocks PD-L1. In certain embodiments, the disclosure relates to methods of using peptides or nanoparticles disclosed herein for the treatment of cancer. In certain embodiments, the disclosure relates to methods of using nanoparticles disclosed herein for therapeutic and diagnostic applications.

1 . A peptide comprising NWNRLSPSNQTEKQAAP (SEQ ID NO: 8) or variants thereof and CGAISLHPKAKIEE (SEQ ID NO: 9) or variants thereof. 
     
     
         2 . The peptide of  claim 1 , wherein the variant of SEQ ID NO: 8 has at least 70 or 80 percent sequence identity. 
     
     
         3 . The peptide of  claim 1 , wherein the variant of SEQ ID NO: 8 has up to 3 amino acid substitutions, deletions, and/or additions. 
     
     
         4 . The peptide of  claim 1 , wherein the variant of SEQ ID NO: 9 has at least 80 percent sequence identity. 
     
     
         5 . The peptide of  claim 1 , wherein the variant of SEQ ID NO: 9 has up to 2 amino acid substitutions, deletions, and/or additions. 
     
     
         6 . The peptide of  claim 1 , wherein peptide comprises SEQ ID NO: 2. 
     
     
         7 . A nanoparticle comprising the peptide of  claim 1 . 
     
     
         8 . The nanoparticle of  claim 7 , further comprising conjugated ATF or ATF-MMP14 and/or a chemotherapy agent. 
     
     
         9 . The nanoparticle of  claim 7 , further comprising a Indoleamine-2,3-dioxygenase (IDO) inhibitor such as indoximod or epacadostat. 
     
     
         10 . A pharmaceutical composition comprising a nanoparticle of  claim 7  and a pharmaceutically acceptable excipient. 
     
     
         11 . A method of treating cancer comprising administering an effective amount of a nanoparticle of  claim 7  to a subject in need thereof. 
     
     
         12 . The method of  claim 11 , wherein the cancer is carcinoma, lymphoma, blastoma, sarcoma, and leukemia, non-small cell lung, squamous cell, small-cell lung, peritoneum, hepatocellular, gastrointestinal, pancreatic, glioma, cervical, ovarian, liver, bladder, hepatoma, breast, colon, colorectal, endometrial or uterine, salivary gland, kidney, liver, prostate, vulval, thyroid, hepatic, leukemia and other lymphoproliferative disorders, and various types of head and neck. 
     
     
         13 . A nucleic acid sequence comprising a sequence encoding the peptide (SEQ ID NO: 8 or 9) from  claim 1 . 
     
     
         14 . A vector comprising a nucleic acid sequence of  claim 13 . 
     
     
         15 . A cell comprising a vector of  claim 14 .