G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells
| Autor: | Pm, Anderson, Crist W, Hasz D, Aj, Carroll, Myers DE, Fatih M. Uckun |
|---|---|
| Předmět: |
Cytotoxicity
Immunologic B-Lymphocytes CD3 Complex Chromosomes Human Pair 11 Immunology Antigens CD19 Antibodies Monoclonal hemic and immune systems Cell Biology Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphocyte Activation Biochemistry Translocation Genetic Antigens Differentiation B-Lymphocyte Antigens CD Bone Marrow hemic and lymphatic diseases Humans Interleukin-2 Chromosomes Human Pair 4 Child |
| Zdroj: | Europe PubMed Central |
| Popis: | A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2- activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T- ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type- specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell- mediated lysis of t(4;11) ALL blasts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|