Fred Hutchinson Cancer Center

Boris Masinovsky

William M Gallatin

Paul J Simmons

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

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.

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Bellevue, WA, United States of America

Boris Masinovsky