Methods of producing aggregate-free monomeric diphtheria toxin fusion proteins and therapeutic uses
The present invention is a DNA expression vector comprising: a toxP; a mutant toxO that blocks Fe-mediated regulation of gene expression; and a DNA sequence encoding a protein, wherein the toxP and the mutant toxO regulate expression of the DNA segment encoding the protein. It is preferred that DNA expression vectors of the present invention include DNA sequences encoding a signal peptide so that a protein expressed is attached to the signal peptide prior to processing. Novel proteins are produced off of the DNA expression vector of the present invention.
1. A fusion protein having an amino acid sequence selected from the group consisting of SEQ ID NOs: 12, 14, 15, and 43.
2. A pharmaceutical composition comprising a fusion protein of claim 1 .
3. The pharmaceutical composition of claim 2 , and at least one or more chemotherapy agents.
4. A protein having the amino acid sequence of any one of SEQ ID NOs: 12, 14, 15, and 43.
5. The pharmaceutical composition comprising a fusion protein of claim 1 , and at least one or more chemotherapy agents.
6. The pharmaceutical composition of claim 3 , wherein the other chemotherapy agent is selected from the group consisting from isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, ethambutol, streptomycin, amikacin, kanamycin, ethionamide, protionamide, terizidone, thiacetazone, cycloserine, caperomycin, para-amino salicylic acid (PAS), viomycin, linezolid, tedezolid, amoxicillin-clavulanic acid, meropenem, imipenem, clarithromycin, or clofazimine.
7. The pharmaceutical composition of claim 2 comprising one or more antimicrobial agents.