| 摘要 |
The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606, wherein the amino acid residues are defined by reference to SEQ ID NO: 1. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention. |
| 主权项 |
1. A Pseudomonas exotoxin A (PE) comprising a PE amino acid sequence wherein one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606 as defined by reference to SEQ ID NO: 1 are, independently, substituted, with the proviso that when the amino acid residue at position 516 is substituted with alanine, at least one of amino acid residues E420, D463, Y481, R563, D581, D589, and K606 is substituted,
wherein the PE has a further substitution of one or more amino acid residues within one or more B cell epitopes, and the further substitution for an amino acid within one or more B-cell epitopes is a substitution of, independently, one or more of amino acid residues E282, E285, P290, R313, N314, P319, D324, E327, E331, Q332, D403, D406, R412, R427, E431, R432, R458, D461, R467, R490, R505, R513, E522, R538, E548, R551, R576, Q592, and L597 as defined by reference to SEQ ID NO: 1, and wherein the PE optionally has a further substitution of one or more amino acid residues within one or more T-cell epitopes and/or a deletion of one or more continuous amino acid residues of residues 1-273 and 285-394 as defined by SEQ ID NO: 1. |
