Enhanced killing of B lymphoma cells by granulocyte colony-stimulating factor-primed effector cells and Hu1D10--a humanized human leucocyte antigen DR antibody.

Abstract

Antibody-based approaches have become a novel treatment modality for lymphoma patients. Humanized 1D10 (Hu1D10; Remitogen) is among the antibodies that are currently under evaluation in phase II clinical trials in lymphoma patients. The 1D10 antibody is directed against a polymorphic epitope on the beta-chain of human leucocyte antigen (HLA) class II. We found expression of the 1D10 epitope on B cells and monocytes from approximately 50% of healthy donors. Analyses of 1D10 expression on malignant cells revealed that approximately half of the HLA class II-positive haematological malignancies expressed the 1D10 epitope. In whole blood antibody-dependent cellular cytotoxicity (ADCC) assays, Hu1D10 was more effective than rituxan in killing malignant ARH-77 B cells. Interestingly, Hu1D10-mediated lymphoma cell lysis was significantly enhanced when blood from granulocyte colony-stimulating factor (G-CSF)-treated patients was compared with blood from healthy controls. Analyses of the relevant effector cell populations revealed that FcgammaRI (CD64)-positive polymorphonuclear cells were critical for enhanced Hu1D10-mediated lymphoma killing during G-CSF therapy, while the same effector cell population induced only marginal lysis with rituxan. Furthermore, Hu1D10 was highly effective in inducing apoptosis in primary lymphoma cells from B chronic lymphocytic leukaemia patients. These preclinical results form the basis for a phase I/II clinical trial of Hu1D10 in combination with G-CSF.

• Authors: Bernhard Stockmeyer, Martin Schiller, Roland Repp, Hanns-Martin Lorenz, Joachim R Kalden, Martin Gramatzki, Thomas Valerius
• Journal: British journal of haematology (Br J Haematol) Vol. 118 Issue 4 Pg. 959-67 (Sep 2002) ISSN: 0007-1048 [Print] England
• PMID: 12199773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20
• Antineoplastic Agents
• Receptors, IgG
• Granulocyte Colony-Stimulating Factor
• Rituximab

Topics

• Adoptive Transfer
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20 (immunology)
• Antineoplastic Agents (therapeutic use)
• Apoptosis
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Humans
• Lymphoma, B-Cell (immunology, pathology, therapy)
• Mice
• Receptors, IgG (immunology)
• Rituximab
• T-Lymphocytes, Regulatory (immunology)
• Tumor Cells, Cultured