Affiliations: [a] Department of Molecular Discovery Technologies, Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA | [b] Department of ImmunoBiology, Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA | [c] Department of Oncology, Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA | [d] Department of Protein Engineering, Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA
Correspondence:
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Corresponding author: Mail code R32, 145 King of Prussia Rd, Radnor, PA 19087, USA. Tel.: +1 610 651 7380; Fax: +1 610 240 8150.
Abstract: The human CCL2 chemokine is implicated in many chronic inflammatory conditions. In the mouse, there are two CCL2 homologues, CCL2 (MCP-1/JE) and CCL12 (MCP-5). Both are potent monocyte chemoattractants and bind to and activate the same receptor, CCR2. The overlapping activities of these chemokines complicate the design of mouse model studies that are intended to mimic human disease. To study the roles of CCL2 and CCL12, we generated neutralizing antibodies specific to each chemokine. Consistent with binding and affinity analyses, the antibodies specifically inhibited CCL2- or CCL12- mediated Ca2+ mobilization in THP-1 cells. When tested in nude mice bearing human PANC-1 pancreatic tumor cells in Matrigel™ plugs, CCL2 and CCL12 antibodies potently inhibited tumor angiogenesis, indicating that both CCL2 and CCL12 may contribute to tumor angiogenesis.
