Abstract |
We have investigated the anti- leukemia effect that is exerted by the murine anti-CD7 antibody HB2 in a severe combined immunodeficient (SCID) mouse model of human T-cell acute lymphoblastic leukemia ( T-ALL) and determined the contribution that this antibody effect makes to the therapeutic potency of a saporin immunotoxin (IT) constructed with the same antibody. The anti- leukemia effect is not exerted through complement-mediated lysis or through direct growth-inhibitory signaling after binding of antibody to the CD7 molecule on the T-ALL cell surface but rather through antibody-dependent cellular cytotoxicity (ADCC). Thus, the in vivo depletion of SCID mice of their natural killer cells almost completely abolishes the therapeutic effect of native HB2 anti-CD7 antibody and moreover significantly reduces the in vivo therapeutic performance of the anti-CD7 HB2-SAPORIN IT. Furthermore, an IT constructed with the F(ab')2 fragment of the same anti-CD7 antibody (HB2-F(ab')2-SAPORIN), which is incapable of recruiting natural killer cells, performed significantly less well therapeutically than HB2-SAPORIN IT. There was also a significant improvement in the therapeutic performance of the HB2-F(ab')2-SAPORIN IT in SCID-HSB-2 mice when used in combination with intact HB2 antibody, presumably through restoration of an ADCC attack on the target HSB-2 cell. These combined data indicate that ADCC in the SCID mouse does contribute additively together with toxin to the in vivo therapeutic potency of the HB2-SAPORIN IT directed against this human T-ALL cell line and that this has potentially important implications for the utility of this and other related classes of immunotherapeutic in human therapy.
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Authors | D J Flavell, S Warnes, A Noss, S U Flavell |
Journal | Cancer research
(Cancer Res)
Vol. 58
Issue 24
Pg. 5787-94
(Dec 15 1998)
ISSN: 0008-5472 [Print] United States |
PMID | 9865737
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Antigens, CD7
- Immunoconjugates
- Immunoglobulin Fab Fragments
- Immunotoxins
- Plant Proteins
- Protein Synthesis Inhibitors
- Ribosome Inactivating Proteins, Type 1
- N-Glycosyl Hydrolases
- Saporins
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Topics |
- Animals
- Antibodies
(metabolism)
- Antibody-Dependent Cell Cytotoxicity
- Antigens, CD7
(immunology)
- Cell Division
(drug effects)
- Immunoconjugates
(therapeutic use)
- Immunoglobulin Fab Fragments
(pharmacology)
- Immunophenotyping
- Immunotoxins
(administration & dosage)
- Leukemia-Lymphoma, Adult T-Cell
(therapy)
- Mice
- Mice, SCID
- N-Glycosyl Hydrolases
- Plant Proteins
(administration & dosage)
- Protein Synthesis Inhibitors
(pharmacology)
- Ribosome Inactivating Proteins, Type 1
- Saporins
- Spleen
(cytology)
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