Clinical Experience with CD3 X CD19 Bispecific Antibodies in Patients with B Cell Malignancies
| Autor: | Anet Van Dijk, Roel A. de Weger, Anja A. van Houten, Mike Clark, Jenny M. Phillips, Gijsbert C. de Gast, I.-A. Haagen, Bert J. E. G. Bast, S. C. Klein |
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| Rok vydání: | 1995 |
| Předmět: |
Lymphoma
B-Cell Fever T-Lymphocytes Chronic lymphocytic leukemia T cell Antigens CD19 Immunology Pharmacology Lymphocyte Activation Muromonab-CD3 Mice Antigen Antibody Specificity Antibodies Bispecific medicine Animals Humans Immunologic Factors Clonogenic assay B cell B-Lymphocytes Tumor Necrosis Factor-alpha business.industry Hematology medicine.disease Combined Modality Therapy Leukemia Lymphocytic Chronic B-Cell Rats Leukemia medicine.anatomical_structure Neoplastic Stem Cells Interleukin-2 Chills medicine.symptom business medicine.drug |
| Zdroj: | Journal of Hematotherapy. 4:433-437 |
| ISSN: | 1061-6128 |
| DOI: | 10.1089/scd.1.1995.4.433 |
| Popis: | In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy. |
| Databáze: | OpenAIRE |
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