Prevention of mantle lymphoma tumor establishment by routing transferrin receptor toward lysosomal compartments.

Abstract

Mantle cell lymphoma (MCL) is one of the most frequent of the newly recognized non-Hodgkin's lymphomas. The major problem of MCL therapy is the occurrence of relapse and subsequent resistance to chemotherapy and immunotherapy in virtually all cases. Here, we show that one injection of anti-human transferrin receptor (TfR) monoclonal antibody A24 totally prevented xenografted MCL tumor establishment in nude mice. It also delayed and inhibited tumor progression of established tumors, prolonging mice survival. In vitro, A24 induced up to 85% reduction of MCL cell proliferation (IC(50) = 3.75 nmol/L) independently of antibody aggregation, complement-dependent or antibody-dependent cell-mediated cytotoxicity. A24 induced MCL cell apoptosis through caspase-3 and caspase-9 activation, either alone or synergistically with chemotherapeutic agents. A24 induced TfR endocytosis via the clathrin adaptor protein-2 complex pathway followed by transport to lysosomal compartments. Therefore, A24-based therapies alone or in association with classic chemotherapies could provide a new alternative strategy against MCL, particularly in relapsing cases.

• Authors: Yves Lepelletier, Valérie Camara-Clayette, Hulin Jin, Aurélie Hermant, Séverine Coulon, Michaël Dussiot, Michelle Arcos-Fajardo, Cédric Baude, Danielle Canionni, Richard Delarue, Nicole Brousse, Philippe Benaroch, Marc Benhamou, Vincent Ribrag, Renato C Monteiro, Ivan C Moura, Olivier Hermine
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 3 Pg. 1145-54 (Feb 01 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17283149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Receptors, Transferrin

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Endocytosis (drug effects)
• Female
• Humans
• Immunization, Passive (methods)
• Lymph Nodes (metabolism, pathology)
• Lymphoma, Mantle-Cell (metabolism, pathology, prevention & control)
• Lysosomes (metabolism)
• Mice
• Mice, Nude
• Receptors, Transferrin (immunology, metabolism)
• Xenograft Model Antitumor Assays