IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells Journal Article
| Authors: | Czuczman, M. S.; Garin-Chesa, P.; Lemoli, R. M.; Scheinberg, D. A. |
| Article Title: | IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells |
| Abstract: | 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 LD50 of 100 ng/ml. At this mAb concentration, fewer than 4% of more than 105 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. © 1993 Springer-Verlag. |
| Keywords: | immunohistochemistry; clinical article; human cell; animal; mice; cell cycle; cancer immunotherapy; mice, inbred balb c; b-lymphocytes; monoclonal antibodies; monoclonal antibody; b cell lymphoma; lymphocyte activation; antibodies, monoclonal; antigens, neoplasm; hematopoietic stem cells; cytotoxicity, immunologic; up-regulation; burkitt lymphoma; complement dependent cytotoxicity; complement; immunoglobulin m; b cell leukemia; antigen-antibody reactions; igm; complement-dependent cytotoxicity; human; priority journal; article; support, non-u.s. gov't; antigen upregulation; b cell neoplasms |
| Journal Title: | Cancer Immunology, Immunotherapy |
| Volume: | 36 |
| Issue: | 6 |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Date Published: | 1993-11-01 |
| Start Page: | 387 |
| End Page: | 396 |
| Language: | English |
| DOI: | 10.1007/bf01742255 |
| PUBMED: | 8500111 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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18Lemoli
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