Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin

US6465251B1 · kind B1 · utility

Assignee

• DANA-FARBER CANCER INSTITUTE, INC. · US

Inventors

• Joachim L. Schultze · Pulheim, DE
• Gordon J. Freeman · Brookline, US
• John Gribben · Newry, GB
• Lee M. Nadler · Newton, US

Key dates

• Filing date: Nov 13, 1996
• Grant date: Oct 15, 2002
• Expiry date: Nov 13, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2501/52
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF&bgr;.