title: An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies.
abstract: Moxetumomab pasudotox (HA22) is a recombinant immunotoxin, now in clinical trials, that combines an anti-CD22-Fv with a 38-kDa fragment of Pseudomonas exotoxin A. To produce a less immunogenic molecule without reducing the half-life in circulation, we constructed LMB11 combining an anti-CD22 Fab with a less immunogenic version of PE38. We found that LMB11 retains full activity toward CD22-expressing cells. In mice, the half-life of LMB11 is 29 min and the antitumor activity of LMB11 is better than that of HA22. Because it can be safely given at much higher doses, LMB11 produced complete tumor remissions in 7/7 mice.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Bera
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Onda
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA. Electronic address: pastani@mail.nih.gov.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D005098:Exotoxins; D005260:Female; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology*; D007938:Leukemia; D051379:Mice; D008807:Mice, Inbred BALB C; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; C541974:immunotoxin HA22
keywords: B-cell malignancies; Less immunogenic PE38; Moxetumomab pasudotox