Fred Hutchinson Cancer Center

Icos Corporation

State of Oregon

William M Gallatin

Paul J Simmons

Boris Masinovsky

John D Scott

Monique L Howard

Vincent M Coghlan

Monica Van Der Vieren

A therapeutic method of modulating the immune response, by administering to a patient an amount of IL-4 effective to promote peripheral blood lymphocyte adhesion to microvascular endothelial cells in lymphoid organs. The IL-4 is preferably coadministered with IL-1&#x3b2;. An improved method of screening a cell line for the production of a binding partner that binds with a cell adhesion molecule, by contacting the binding partner with IL4-activated and nonactivated microvascular endothelial cells, and selecting binding partners that bind to the IL4-activated microvascular endothelial cells but not to the nonactivated microvascular endothelial cells. The selected binding partners may thereafter be tested for the ability to block lymphocyte binding to cytokine-activated endothelial cells. The binding partners are preferably also characterized by binding to human VCAM-1 and to IL4- or TNF&#x3b1;-activated bone marrow stromal cells. A representative embodiment is mAb 6G10 produced by hybridoma ATTC No. HB10519. A therapeutic method of modulating the immune response in a patient, by administering to the patient an agent that specifically binds to IL4-activated microvascular endothelial cells, in an amount effective to impede transmigration of lymphocytes that specifically bind to VCAM-1 from blood across postcapillary venules.

Methods of blocking the interaction between stromal cells and hemopoietic cells with anti-VCAM-1 antibodies

A therapeutic method of modulating the immune response, by administering to a patient an amount of IL-4 effective to promote peripheral blood lymphocyte adhesion to microvascular endothelial cells in lymphoid organs. The IL-4 is preferably coadministered with IL-1.beta.. An improved method of screening a cell line for the production of a binding partner that binds with a cell adhesion molecule, by contacting the binding partner with IL4-activated and nonactivated microvascular endothelial cells, and selecting binding partners that bind to the IL4-activated microvascular endothelial cells but not to the nonactivated microvascular endothelial cells. The selected binding partners may thereafter be tested for the ability to block lymphocyte binding to cytokine-activated endothelial cells. The binding partners are preferably also characterized by binding to human VCAM-1 and to IL4- or TNF.alpha.-activated bone marrow stromal cells. A representative embodiment is mAb 6G10 produced by hybridoma ATTC No. HB 10519. A therapeutic method of modulating the immune response in a patient, by administering to the patient an agent that specifically binds to IL4-activated microvascular endothelial cells, in an amount effective to impede transmigration of lymphocytes that specifically bind to VCAM-1 from blood across postcapillary venules.

Methods for using agents that bind to VCAM-1

Methods of isolating and detecting bone marrow stromal cells with

The present invention provides compositions and methods useful for isolating calcineurin as well as inhibiting calcineurin activity. The compositions are peptides that contain regions that are homologous to calcineurin-binding regions of AKAP 79. Also provided are methods for determining if a cell contains a calcineurin-binding and PKA-binding anchoring protein that are useful for identifying additional proteins that bind both calcineurin and PKA.

Calcineurin inhibitory compounds and anchoring protein

DNA encoding a novel human .beta..sub.2 integrin .alpha. subunit polypeptide, designated .alpha..sub.d, is disclosed along with methods and materials for production of the same by recombinant procedures. Binding molecules specific for .alpha..sub.d are also disclosed as useful for modulating the biological activities of .alpha..sub.d.

Human .beta..sub.2 integrin .alpha. subunit

An improved method of screening a cell line for the production of a binding partner that binds with a cell-surface molecule, by contacting the binding partner with IL4-activated and nonactivated human bone marrow stromal cells, and selecting binding partners that bind to the IL4-activated human bone marrow stromal cells but not to the nonactivated human bone marrow stromal cells. The selected binding partners may thereafter be tested for the ability to block CD34.sup.+ bone marrow cell binding to IL4-activated human bone marrow stromal cells. The binding partners are preferably also characterized by binding to human VCAM-1. A representative embodiment is mAb 6G10 produced by hybridoma ATTC No. HB 10519.

Growing community of inventors

Mercer Island, WA, United States of America

William M Gallatin