| Autor: |
Czuczman, Myron, Garin-Chesa, Pilar, Lemoli, Roberto, Scheinberg, David |
| Zdroj: |
Cancer Immunology, Immunotherapy; Nov1993, Vol. 36 Issue 6, p387-396, 10p |
| Abstrakt: |
Cancer therapy using unconjugated monoclonal antibodies (mAb) has been limited by the lack of immune effector function of the mAb and antigenic modulation. JD118 is a cytotoxic murine IgM mAb with reactivity restricted to a subset of normal B cells, some monocytic series cells, and a large percentage of B cell hematopoietic neoplasms including acute and chronic leukemias and lymphomas. Specificity was determined on several hundred normal and neoplastic, hematopoietic and non-hematopoietic cells and tissues, as well as progenitor cells. JD118 was able to kill fresh human leukemias and lymphomas in the presence of human serum as a complement source with an LD of 100 ng/ml. At this mAb concentration, fewer than 4% of more than 10 available target sites were bound. Killing was not affected by changes in antigen expression observed during the cell cycle nor by loss of cell-surface targets via antigenic modulation. Cytotoxicity could be achieved with human serum diluted as low as 5%, suggesting that complement depletion in vivo should not limit activity. Autologous human serum could be used effectively as a complement source. The JD118 antigen target has not been identified, but it appears to be a glycoprotein. Up-regulation of antigen expression on normal B cells and chronic lymphocytic leukemia cells in vitro resulted in antigen-negative neoplasms becoming positive and thus targets for JD118 killing. The restricted expression, potent cytotoxic characteristics, and potential for up-regulation of its antigen make JD118 a possible candidate for ex vivo autologous bone marrow purging and in vivo therapeutic trials in patients with B cell neoplasms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink