Abstract | PURPOSE: To investigate the activity of SAR3419, a novel humanized anti-CD19 antibody (huB4), conjugated to a cytotoxic maytansine derivative N(2)'-deacetyl-N(2)'-(4-mercapto-4-methyl-1-oxopentyl) maytansine, in preclinical xenograft models for non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: RESULTS: Our results showed that in these chemotherapy-resistant models, SAR3419 was more effective than CHOP ( cyclophosphamide- Adriamycin- vincristine- prednisone) regimen or rituximab. Only treatment with SAR3419 led to survival of the whole group of animals to the end of the experiment (150-155 days) in both models. Higher doses of SAR3419 (15 and 30 mg/kg) were more effective than lower dose of 7.5 mg/kg. The immunoconjugation was necessary because neither huB4 nor DM4 alone had significant activity. Treatment with rituximab resulted in antitumor activity in both models comparable with the low dose of SAR3419. Cyclophosphamide- Adriamycin- vincristine- prednisone alone showed modest activity in both models. Necropsy and tissue staining in the WSU-FSCCL systemic model revealed that all deaths featured leptomeningeal lymphoma in the control and treated groups. Interestingly, some of the animals that survived to the end of the experiment and seemed healthy at time of euthanasia did show microscopic evidence of lymphoma. CONCLUSIONS:
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Authors | Ayad M Al-Katib, Amro Aboukameel, Ramzi Mohammad, Marie-Christine Bissery, Claudia Zuany-Amorim |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 15
Issue 12
Pg. 4038-45
(Jun 15 2009)
ISSN: 1557-3265 [Electronic] United States |
PMID | 19509168
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD19
- Antineoplastic Agents, Phytogenic
- Immunoconjugates
- Immunologic Factors
- Maytansine
- Rituximab
- Vincristine
- Doxorubicin
- Cyclophosphamide
- Prednisone
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Topics |
- Animals
- Antibodies, Monoclonal
(immunology, therapeutic use)
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD19
(metabolism)
- Antineoplastic Agents, Phytogenic
(chemistry, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Cell Line, Tumor
- Cyclophosphamide
(therapeutic use)
- Doxorubicin
(therapeutic use)
- Humans
- Immunoconjugates
(therapeutic use)
- Immunologic Factors
(therapeutic use)
- Lymphoma, Follicular
(drug therapy, pathology)
- Lymphoma, Large B-Cell, Diffuse
(drug therapy, pathology)
- Maytansine
(analogs & derivatives, therapeutic use)
- Mice
- Mice, SCID
- Prednisone
(therapeutic use)
- Rituximab
- Vincristine
(therapeutic use)
- Xenograft Model Antitumor Assays
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