MODULATION OF B-CELL CHEMOATTRACTANT/RECEPTOR INTERACTION AS TREATMENT FOR IMMUNE DISEASE

Abnormal development of lymphoid tissue plays a critical role in many autoimmune diseases, such as rheumatoid arthritis and Graves' disease. In addition, the migration of lymphocytes into diseased lymphoid tissue facilitates the progression of diseases such as AIDS. UCSF researchers have identified a pathway, involved both in the development of lymphoid tissue and in the migration of lymphocytes into lymphoid tissue, which is a potential target for screens for therapeutics to treat these diseases and other immune disorders.

The B-lymphocyte chemoattractant (BLC/BCA1), through its interaction with the G-protein coupled receptor BLR1/CXCR5, is important for the migration of B-cells and a subset of T-cells and macrophages into lymphoid follicles. Recent investigation by UCSF researchers has proven that the BLC/BLR1 pathway is essential for B-cell migration to the spleen and lymph nodes, for the development of lymph nodes and Peyer's patches, and for the establishment of a positive feedback loop with lymphotoxin Lta1b2 to mediate follicular dendritic development and persistent BLC expression. This work and additional studies at UCSF suggest that the interaction between BLC and its receptor, BLR1/CXCR5, may be a useful target for modulation of the normal and ectopic development of lymphoid tissue as well as lymphocyte migration.

Commercial potential:

UCSF holds an issued U.S. patent for screens to identify compounds that will modulate the BLC/BRL1 interaction. Such compounds may be useful for:

• Inhibition of ectopic lymphoid follicle development at sites of chronic inflammation, such as those found in autoimmune diseases such as rheumatoid arthritis and Graves' disease.
• Inhibition of T-cell entry into HIV-laden follicles in order to limit further HIV infection of T-cells in patients with AIDS.
• Augmentation/inhibition of primary immune responses that play important roles in infection, vaccination, autoimmune disease, and transplant rejection.

Intellectual Property:

UCSF has issued U.S. patent 6,110,695 covering methods for identifying agents such as small molecules, peptides, or variants of BLC and BLR1 which modulate BLC/BLR1 polypeptide interactions.

Select References:

Ansel, K.M., Ngo, V.N., Hyman, P.L., Luther, S.A., Forster, R., Sedgwick, J.D., Browning, J.L., Lipp, M. and Cyster, J.G. (2000) A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 406(6793):309-14.

Luther, S.A., Lopez, T., Bai, W., Hanahan, D., and Cyster, J.G. (2000) BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity. 12(5):471-81.

Gunn, M.D., Ngo, V.N., Ansel, K.M., Ekland, E.H., Cyster, J.G., and Williams, L.T. (1998) A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1. Nature 391(6669):799-803.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Joel B. Kirschbaum, Ph.D.
Director & Senior Technology Portfolio Manager
(415) 353-4462 phone
(415) 348-1579 fax
Joel Kirschbaum, Ph.D.

Reference: OTM Case #SF98-026