Purification of heat shock/stress protein cell surface receptors and their use as immunotherapeutic agents

Abstract

The present invention relates to receptors for heat shock proteins (HSPs), such as gp96, Hsp70 and Hsp90. The receptor is associated with the cell membranes of a subset of antigen presenting cells, such as macrophages, dendritic cells. The invention provides methods for identifying and isolating cells that express the heat shock protein receptor, the heat shock protein receptor, antibodies to heat shock protein receptor and nucleic acid molecules encoding heat shock protein receptor, and fragments thereof. The present invention further provides methods of use of the heat shock protein receptor positive cells, heat shock protein receptor protein, heat shock protein receptor antibodies, and heat shock protein receptor gene. Methods for identifying a molecule that enhance or block the function of heat shock protein receptor are included in the invention. The compositions of the invention may be used in various diagnostic and therapeutic applications in the area of cancer and infectious diseases.

Description

[0001] This application claims priority under 35 U.S.C. §119(e) to provisional patent application no. 60 / 103,115, filed Oct. 5, 1998, which is incorporated by reference herein in its entirety.[0002] The invention was made with government support under grant numbers CA44786 and CA64394 awarded by the National Institutes of Health. The government has certain rights in the invention.1. INTRODUCTION [0003] The present invention relates to the cell surface receptors for heat shock proteins (HSPs), such as gp96, Hsp70 and Hsp90, cells that express the Hsp receptor, genes that encode the Hsp receptor, and antibodies and other molecules that bind the receptor. The invention also relates to the diagnostic uses of these molecules in immunotherapy. HSP cell surface receptors recognize and bind to HSPs and are associated with the cell membranes of a subset of macrophages and dendritic cells. HSP cell surface receptors can have uses in the diagnosis and treatment of cancer and proliferative dise...

AI Technical Summary

Benefits of technology

"The present invention is based on the discovery of a receptor that recognizes and binds to heat shock protein. This receptor is associated with the cell membranes of a subset of macrophages, dendritic cells, and possibly other cell types. The invention provides methods for enriching and isolating cells that express the HSP receptor, as well as identifying and isolating nucleic acid molecules encoding the HSP receptor. The HSP receptor can be used for modulating the immune response and identifying molecules that enhance or block its function. The invention also provides methods for using the HSP receptor, HSPR protein, HSPR antibodies, and hspr gene in diagnostic and therapeutic applications in the area of cancer and infectious diseases."

Problems solved by technology

Since only a small number of cancer cells can be obtained from a subject, especially if the cancer is at an early stage, the supply of cancer cells for producing the HSP-peptide complex is often very limited.

However, the process whereby exogenously introduced gp96-peptide complexes elicit the antigen-specific CD8+T cell response is not completely understood since there is no established pathway for the translocation of extracellular antigens into the class I presentation machinery.

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