申请人:JONES Timothy David
公开号:US20130121983A1
公开(公告)日:2013-05-16
Pseudomonas
exotoxin A or “PE” is a 66 kD, highly potent, cytotoxic protein secreted by the bacterium
Pseudomonas aeruginosa
. Various forms of PE have been coupled to other proteins, such as antibodies, to generate therapeutically useful cytotoxin conjugates that selectively target cells of a desired phenotype (such as tumor cells). In the present invention, peptides spanning the sequence of an approximately 38 kD form of
Pseudomonas
exotoxin A protein were analyzed for the presence of immunogenic CD4+ T cell epitopes. Six immunogenic T cell epitopes were identified. Residues were identified within each epitope for introduction of targeted amino acid substitutions to reduce or prevent immunogenic T-cell responses in PE molecules which may be administered to a heterologous host.