Abstract | PURPOSE: EXPERIMENTAL DESIGN: Scid mice received i.v. injections of CD22+ Ramos B-cell lymphoma cells for their systemic dissemination. CMC-544, G5/44, CD33-targeted CMA-676 (control conjugate) or rituximab were given i.p. 3, 9, 15, or 21 days after B-cell lymphoma dissemination. Diseased mice were monitored daily for hind-limb paralysis and death. Histopathological examination of CMC-544-treated and vehicle-treated diseased mice was also performed. RESULTS: Mice with disseminated B-cell lymphoma developed hind-limb paralysis within 35 days. When given up to 15 days after B-cell lymphoma dissemination, CMC-544 extended survival of the diseased mice to >100 days, and these mice were considered cured. CMC-544 was efficacious when given during both the early initiation phase and the late established phase of the disease. A single dose of CMC-544 was effective in delaying the occurrence of hind-limb paralysis. In contrast, neither CMA-676 nor unconjugated G5/44 was effective. Rituximab was effective when given early in the disease process but not when the disease was established. Histopathological analysis revealed B-cell lymphoma infiltration in brain, spinal cord, bone marrow, and kidney in vehicle-treated but not in CMC-544-treated diseased mice. Consistent with its efficacy against the disseminated B-cell lymphoma, CMC-544 also caused regression of established Ramos B-cell lymphoma xenografts in scid mice. CONCLUSIONS:
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Authors | John F DiJoseph, Mary E Goad, Maureen M Dougher, Erwin R Boghaert, Arthur Kunz, Philip R Hamann, Nitin K Damle |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 24
Pg. 8620-9
(Dec 15 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15623646
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD
- Antigens, Differentiation, B-Lymphocyte
- CD22 protein, human
- Cd22 protein, mouse
- Cell Adhesion Molecules
- Immunoconjugates
- Immunoglobulin G
- Lectins
- Sialic Acid Binding Ig-like Lectin 2
- Rituximab
- Inotuzumab Ozogamicin
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Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD
(metabolism)
- Antigens, Differentiation, B-Lymphocyte
(metabolism)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Cell Adhesion Molecules
(metabolism)
- Hindlimb
- Humans
- Immunoconjugates
(therapeutic use)
- Immunoglobulin G
(metabolism)
- Immunotherapy
(methods)
- Inotuzumab Ozogamicin
- Lectins
(metabolism)
- Lymphoma, B-Cell
(metabolism, pathology, therapy)
- Male
- Mice
- Mice, SCID
- Paralysis
(etiology)
- Rituximab
- Sialic Acid Binding Ig-like Lectin 2
- Survival Rate
- Transplantation, Heterologous
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