Fusion proteins and uses thereof
A fusion protein is provided which comprises a first and a second peptide. The first peptide enables the fusion protein to bind to a receptor expressed on a cell, and the second peptide having a cleavage site that enables the fusion protein to kill said cell. The fusion protein is thus useful for the prevention or treatment of an infection caused by a pathogen. Nucleic acids encoding the fusion protein and methods of making and using the fusion protein are also provided.
1 . A fusion protein consisting of the amino acid sequence of SEQ ID NO: 6.
2 . The fusion protein according to claim 1 , wherein the fusion protein has increased potency against cells expressing US28 as compared to the potency against cells expressing CX3CR1.
3 . The fusion protein according to claim 1 , wherein the fusion protein has increased affinity for US28 as compared to the affinity for CX3CR1.
4 . A pharmaceutical composition comprising the fusion protein according to claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.
5 . The pharmaceutical composition according to claim 4 , further comprising one or more further agents.
6 . The pharmaceutical composition according to claim 5 , wherein the agent is an immunosuppressive agent, anti-viral agent, or immunotherapy.
7 . The pharmaceutical composition according to claim 6 , wherein the anti-viral agent is valganciclovir, ganciclovir, cidofovir, leflunomide, prevymis, maribavir, or brincidofovir.
8 . The pharmaceutical composition according to claim 6 , wherein the immunotherapy is T cell therapy.
9 . An isolated nucleic acid molecule encoding the fusion protein according to claim 1 .
10 . A vector comprising the nucleic acid molecule according to claim 9 .
11 . A recombinant host cell comprising the nucleic acid molecule according to claim 9 or the vector according to claim 10 .
12 . A method of treating a CMV infection or a CMV-associated disorder in an individual in need thereof, the method comprising administering a therapeutically effective amount of the fusion protein according to claim 1 or the pharmaceutical composition according to claim 4 to the individual.
13 . The method according to claim 12 , wherein the CMV infection is a latent or lytic CMV infection.
14 . The method according to claim 12 , wherein the CMV infection is an infection in an immune-compromised patient that is a HIV-patient, neonates and immunosuppressive patient, bone marrow transplant patient, solid organ transplant patient, immune therapy patient, cancer patient, intensive care patient, trauma patient, stem cell patient, gene therapy patient, cell therapy patient, geriatric patient, or multimorbid patient.
15 . The method according to claim 12 , wherein the CMV infection is an infection in a patient suffering from a coronary disease or a vascular disease.
16 . The method according to claim 12 , wherein the CMV-associated disorder is cytomegaloviral pneumonitis, cytomegaloviral hepatitis, cytomegaloviral pancreatitis, cytomegaloviral mononucleosis, CMV polyradiculomyelopathy, cytomegalic inclusion body disease, cytomegalovirus colitis, cytomegalovirus esophagitis, cytomegalovirus retinitis, Guillain-Barre syndrome, mucoepidermoid carcinoma, ulcerative colitis, graft versus host disease (GVHD), or solid organ transplant graft versus host disease (SOT-GVHD).
17 . The method according to claim 12 , wherein the individual is a human.
18 . The method according to claim 17 , wherein the human is an immunocompromised patient.
19 . The method according to claim 17 , wherein the human is a child or an adult.
20 . The method according to claim 17 , wherein the fusion protein or the pharmaceutical composition is administered one or more times to a human that is an immunocompromised patient or a human that is in need of a solid organ transplantation or a human that is in need of a hematopoietic stem cell transplantation.
21 . A method of ex vivo treatment of a CMV infection of a solid organ for transplantation or a hematopoietic stem cell for transplantation, the method comprising contacting the fusion protein according to claim 1 or the pharmaceutical composition according to claim 4 with said solid organ or stem cell.