Abstract | BACKGROUND: PROCEDURE: BW704dgA immunotoxins were injected i.p. as a single close (48 microg/mouse) on day 4 or divided into three doses on day 4, 5, and 6 after i.v. inoculation of the human neuroblastoma cell line IMR5-75. RESULTS: The mean survival time (MST) of BW704dgA treated animals was significantly increased (MST 49 days) compared to the control animals treated with irrelevant immunotoxin, unconjugated BW704, or control buffer (MST 33 to 39 days, P < 0.0001), without differences in the application schedules. Anti-CD3xanti-NP antibodies and NP-conjugated GD2-antibodies (BW704-NP) were used in a cytotoxicity assay with cytotoxic T-cells as effectors, and tracer labeled neuroblastoma cell line IMR5 as target cells. Anti-CD3xanti-NP antibodies, together with BW704-NP, showed increased cytotoxic activity compared to the incubation with CD3xanti-NP antibodies alone or with unconjugated anti-GD2. Additionally, a dose-dependent effect of NP-conjugated anti-GD2-antibodies upon the lysis of the target cells could be demonstrated. In this report, we describe two immunotherapeutic approaches using GD2 binding BW704 antibodies, modified as immunotoxin and a bispecific antibody, for the targeting and elimination of neuroblastoma cells. CONCLUSIONS: We envisage a combined immunotherapeutic regimen consisting of BW704dgA mediated stem cell purging, followed by a systemic treatment with anti-CD3xanti-GD2 bispecific antibodies in neuroblastoma.
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Authors | O Manzke, O Russello, C Leenen, V Diehl, H Bohlen, F Berthold |
Journal | Medical and pediatric oncology
(Med Pediatr Oncol)
Vol. 36
Issue 1
Pg. 185-9
(Jan 2001)
ISSN: 0098-1532 [Print] United States |
PMID | 11464879
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bispecific
- Antibodies, Monoclonal
- Antibodies, Neoplasm
- CD3 Complex
- Gangliosides
- Haptens
- Immunotoxins
- Trinitrobenzenes
- ganglioside, GD2
- Ricin
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Topics |
- Animals
- Antibodies, Bispecific
(immunology, therapeutic use)
- Antibodies, Monoclonal
(immunology, therapeutic use)
- Antibodies, Neoplasm
(immunology, therapeutic use)
- Antibody Specificity
- CD3 Complex
(immunology)
- Gangliosides
(immunology)
- Haptens
(immunology)
- Humans
- Immunotherapy
- Immunotoxins
(therapeutic use)
- Mice
- Mice, SCID
- Neuroblastoma
(drug therapy, immunology, therapy)
- Ricin
(analogs & derivatives, therapeutic use)
- T-Lymphocytes, Cytotoxic
- Trinitrobenzenes
(immunology)
- Tumor Cells, Cultured
(drug effects, transplantation)
- Xenograft Model Antitumor Assays
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