IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells

Myron S. Czuczman, Pilar Garin-Chesa, Roberto M. Lemoli, David A. Scheinberg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume36
Issue number6
DOIs
Publication statusPublished - Nov 1993

Keywords

  • Antigen upregulation
  • B cell neoplasms
  • Complement-dependent cytotoxicity
  • IgM
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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