Fusion proteins having a toxin and cancer marker, nanoparticles, and uses related thereto
AssigneeEmory University
InventorsLily Yang, Xiangxue Guo, Hui Mao, Wei Chen
Life of this patent
Estimating the term…
Abstract
This disclosure relates to nanoparticles coated with fusion proteins comprising a domain that binds a cancer marker and a domain comprising a toxic polypeptide. In certain embodiments, the targeted cancer marker is urokinase plasminogen activator receptor (uPAR) insulin-like growth factor 1 receptor (IGF1R), EGFR, HER2, and/or other member of the ErbB family of receptors. In certain embodiments, the molecule that binds a cancer marker is an amino terminal fragment of uPA or variant capable of binding uPAR and/or IGF1 or variant capable of binding IGF1R. In certain embodiments, the toxic polypeptide is a bacterial exotoxin.
Claims12
A nanoparticle coated with a fusion peptide comprising a first domain having a single-chain anti-EGFR antibody sequence and the second domain of a toxin, and wherein the nanoparticle is further coated with a molecule that binds insulin-like growth factor 1 receptor;
- and
- wherein the fusion peptide comprises the amino acid sequence of
- (SEQ ID NO:
- 5)
- TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNR
- ATGIPARFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPITFGQGTRL
- EIKRSSGGGGSGAPEGGSLAALTAHQACHLPLETFTRHRQPRGWEQLEQC
- GYPVQRLVALYLAARLSWNQVDQVIRNALASPGSGGDLGEAIREQPEQAR
- LALTLAAAESERFVRQGTGNDEAGAANGPADSGDALLERNYPTGAEFLGD
- GGDVSFSTRGTQNWTVERLLQAHRQLEERGYVFVGYHGTFLEAAQSIVFG
- GVRARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLRVYV
- PRSSLPGFYRTSLTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLE
- TILGWPLAERTVVIPSAIPTDPRNVGGDLDPSSIPDKEQAISALPDYASQ
- PGKPPKDEL.
A method of treating cancer comprising administering an effective amount of a nanoparticle comprising a chemotherapy agent to a subject in need thereof,
- wherein the nanoparticle is coated with a fusion peptide comprising a first domain having a single-chain anti-EGFR antibody sequence and the second domain of a toxin, and wherein the nanoparticle is further coated with a molecule that binds insulin-like growth factor 1 receptor;
- and
- wherein the fusion peptide comprises the amino acid sequence of
- (SEQ ID NO:
- 5)
- TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNR
- ATGIPARFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPITFGQGTRL
- EIKRSSGGGGSGAPEGGSLAALTAHQACHLPLETFTRHRQPRGWEQLEQC
- GYPVQRLVALYLAARLSWNQVDQVIRNALASPGSGGDLGEAIREQPEQAR
- LALTLAAAESERFVRQGTGNDEAGAANGPADSGDALLERNYPTGAEFLGD
- GGDVSFSTRGTQNWTVERLLQAHRQLEERGYVFVGYHGTFLEAAQSIVFG
- GVRARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLRVYV
- PRSSLPGFYRTSLTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLE
- TILGWPLAERTVVIPSAIPTDPRNVGGDLDPSSIPDKEQAISALPDYASQ
- PGKPPKDEL.
A nucleic acid sequence comprising a sequence encoding the fusion protein having the amino acid sequence of
- (SEQ ID NO:
- 5)
- TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNR
- ATGIPARFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPITFGQGTRL
- EIKRSSGGGGSGAPEGGSLAALTAHQACHLPLETFTRHRQPRGWEQLEQC
- GYPVQRLVALYLAARLSWNQVDQVIRNALASPGSGGDLGEAIREQPEQAR
- LALTLAAAESERFVRQGTGNDEAGAANGPADSGDALLERNYPTGAEFLGD
- GGDVSFSTRGTQNWTVERLLQAHRQLEERGYVFVGYHGTFLEAAQSIVFG
- GVRARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLRVYV
- PRSSLPGFYRTSLTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLE
- TILGWPLAERTVVIPSAIPTDPRNVGGDLDPSSIPDKEQAISALPDYASQ
- PGKPPKDEL.
Dependencies are inferred from the claim text.