In vivo cell surface engineering

Abstract

The present invention provides methods and compositions for the in vivo engineering of cell surfaces, such as tumor cell surfaces, with one or more immune co-stimulatory polypeptides. The methods, compositions and engineered cells are useful, for example, to stimulate an immune response against the cells. When the engineered cell surfaces are tumor cell surfaces, the methods, compositions and engineered cells are useful for improving a patient's immune response against the cancer and for reducing tumor size and inhibiting tumor growth.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims the benefit of the filing dates of the following U.S. provisional applications: 60 / 748,177 (filed Dec. 8, 2005); 60 / 771,179 (filed Feb. 6, 2006); 60 / 799,643 (filed May 12, 2006); and 60 / 863,173 (filed Oct. 27, 2006). Each of the foregoing applications is incorporated by reference herein in its entirety.FIELD OF THE INVENTION [0002] The present invention generally relates to methods for in vivo engineering of cell surfaces by displaying one or more exogenous immunostimulatory molecules thereon, for the purposes of stimulating an immune response against the cells. Compositions for effecting the engineering also are provided. BACKGROUND OF THE INVENTION [0003] Approaches directed to boosting a host's immune response to address diseases and conditions characterized by a deficiency in immunity or resolvable by a more aggressive immune response have been extensively described. An exemplary such disease or condit...

AI Technical Summary

Benefits of technology

"The present invention provides methods for engineering the surface of cells to display immune co-stimulatory polypeptides, such as CD86, ICOSL, PD-L1, PD-L2, B7-H3, B7-H4, OX40L, and others. The methods involve contacting cells with a bifunctional molecule that binds to the cell surface and a molecule that binds to the same member of a binding pair. The immune co-stimulatory polypeptides can be displayed on the cell surface via binding between the two molecules. The invention also provides pharmaceutical compositions and methods for treating tumors or other disease states by administering the bifunctional molecule to an individual. The technical effects of the invention include improved methods for engineering cell surfaces with immune co-stimulatory polypeptides and compositions for treating disease states."

Problems solved by technology

Approaching cancer treatment with surgery, chemotherapy and radiotherapy is commonly used but these approaches are appreciated to lack tumor specificity, resulting in adverse side effects and less than satisfactory clinical responses.

However, this approach may be undermined if the cancer cells no longer express the particular antigen and / or if the tumor is able to suppress or tolerize the immune response.

Several hurdles are associated with this approach, such as the need for a considerable tumor mass to prepare the vaccine, difficulties associated with the genetic manipulation of primary tumor cells, and the very long amount of time (weeks to months) required for vaccine preparation for gene therapy based approaches.

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