Abstract |
Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77. Daudi expresses high levels of CD22, whereas NALM-6 and ARH-77 express low levels of CD22. The IgG-RFB4-A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 x 10(-12) M and 50% of NALM-6 and ARH-77 cells at concentrations of 1.5 to 2.1 x 10(-11) M. IgG-RFB4-A was 10-30 times more toxic to Daudi cells than were the IgG-As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT-As constructed from the Fab' fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG-A counterparts. Fab'-RFB4-A was twice as toxic to Daudi cells as ricin, whereas the other Fab'-As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio-iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3-10 times more strongly than the other antibodies, whereas the Fab'-RFB4 bound 1.2 to 3.5 times more strongly than the Fab' fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4-As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22-I and HD6 cross-react with certain normal human tissues lacking cells of B-cell lineage, whereas UV22-2 and RFB4 are B-cell-specific. This fact, together with its superior potency as an IT-A, suggests that RFB4 is the antibody of choice for preparing Fab'-As or IgG-As for in vivo therapy of human B-cell leukemias and lymphomas.
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Authors | G L Shen, J L Li, M A Ghetie, V Ghetie, R D May, M Till, A N Brown, M Relf, P Knowles, J W Uhr |
Journal | International journal of cancer
(Int J Cancer)
Vol. 42
Issue 5
Pg. 792-7
(Nov 15 1988)
ISSN: 0020-7136 [Print] United States |
PMID | 3263328
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies
- Antigens, CD
- Antigens, Differentiation, B-Lymphocyte
- CD22 protein, human
- Cd22 protein, mouse
- Cell Adhesion Molecules
- Immunoglobulin Fab Fragments
- Immunotoxins
- Lectins
- Sialic Acid Binding Ig-like Lectin 2
- Ricin
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Topics |
- Animals
- Antibodies
- Antigens, CD
- Antigens, Differentiation, B-Lymphocyte
(immunology)
- Cell Adhesion Molecules
- Cell Line
- Humans
- Immunoglobulin Fab Fragments
(metabolism)
- Immunotoxins
(therapeutic use)
- Lectins
- Leukemia, B-Cell
(therapy)
- Lymphoma
(therapy)
- Mice
- Ricin
(immunology)
- Sialic Acid Binding Ig-like Lectin 2
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