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An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies
Tapan K Bera1, Masanori Onda1, Robert J Kreitman1
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA.
Leukemia Research
|August 17, 2014
Summary
LMB11, a novel immunotoxin targeting CD22, shows improved anti-tumor activity and safety over HA22. This engineered antibody fragment achieved complete tumor remission in all treated mice, offering a promising therapeutic advancement.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Moxetumomab pasudotox (HA22) is a recombinant immunotoxin targeting CD22, currently in clinical trials.
- HA22 combines an anti-CD22 fragment with a Pseudomonas exotoxin A (PE) fragment.
Purpose of the Study:
- To engineer a less immunogenic immunotoxin with retained efficacy and circulation half-life.
- To evaluate the anti-tumor activity and safety profile of the novel immunotoxin LMB11 compared to HA22.
Main Methods:
- Constructed LMB11 by combining an anti-CD22 Fab with a modified, less immunogenic PE38 fragment.
- Assessed LMB11 activity against CD22-expressing cells in vitro.
- Determined LMB11 half-life and anti-tumor efficacy in murine models.
Main Results:
- LMB11 demonstrated full activity against CD22-expressing cells.
- LMB11 exhibited a half-life of 29 minutes in mice.
- LMB11 showed superior anti-tumor activity compared to HA22, achieving complete tumor remission in all (7/7) mice at higher doses.
Conclusions:
- LMB11 is a potent and less immunogenic anti-CD22 immunotoxin.
- The enhanced safety profile allows for higher, more effective dosing.
- LMB11 represents a promising therapeutic candidate for CD22-expressing malignancies.
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