Monoclonal antibody DLC‐48: An effective reagent for use in the depletion of malignant lymphoma from human bone marrow

Abstract

A combination of large-cell lymphoma cell lines was used as immunogen in the production of DLC-48, a mouse monoclonal antibody (MAb) to a B-cell-associated antigen. This reagent identifies a protein found on a majority of peripheral blood B-cells, B-cell derived tumor cell lines, and lymphoma biopsy specimens. In reactive lymph-node sections, DLC-48 stains both germinal center and mantle zone B-lymphocytes when the immunoperoxidase technique is used. DLC-48 is an IgM, and is highly cytotoxic in the presence of human serum complement. The conditions for complement-mediated cytotoxicity were first optimized by utilizing the chromium-release assay with 2 large-cell lymphoma cell lines, and were then applied to the treatment of the cell lines prior to cloning in agar. A single treatment with antibody and human serum eliminated 4 orders of magnitude of target cells. The cytolytic activity of this antibody was not inhibited by the presence of a 20-fold excess of normal human bone marrow. Treatment with antibody and autologous serum did not affect the growth of human hematopoietic progenitor cells (CFU-GEMM and CFU-GM). These results suggest that DLC-48, either alone or in combination with other MAb reagents, should be effective in eliminating malignant cells of B-lineage from human bone marrow for purposes of autologous bone-marrow transplantation.

Efficient B Cell Depletion via Diphtheria Toxin in CD19-Cre/iDTR Mice

“…It results in the reduction of autoantibodies [1]–[5] but also affects autoimmune diseases through unknown mechanisms as seen in multiple sclerosis [6]–[9]. In addition, B cell depletion is used as therapy in lymphomas [10]–[15]. Consequently, nowadays depletion of B cells is a common therapy in clinical routine and especially anti-CD20 antibodies are commonly used [16]–[18].…”