The Scripps Research Institute

Janssen Pharmaceutica Nv

Ortho-mcneil Pharmaceutical Corp.

Janssen Pharmaceuticals, Inc.

Didier J Leturcq

Ann M Moriarty

Richard J Ulevitch

Peter S Tobias

Per A Peterson

Michael R Jackson

Zeling Cai

Juli Degraw

John C Mathison

Theo Kirkland

Wei-Xing Shi

Jonathan Sprent

Anders Brunmark

Xilian Yue

Alain Luxembourg

Karen Kabat Stegman

Jon M Richards

Marja Heiskala

T cell responses are often diminished in humans with a compromised immune system. We have developed a method to isolate, stimulate and expand na&#xef;ve cytotoxic T lymphocyte precursors (CTLp) to antigen-specific effectors, capable of lysing tumor cells in vivo. This ex vivo protocol produces fully functional effectors. Artificial antigen presenting cells (AAPCs;) transfected with human HLA class I and defined accessory molecules, are used to stimulate CD8T cells from both normal donors and cancer patients. The class I molecules expressed to a high density on the surface of thecells are empty, allowing for efficient loading of multiple peptides that results in the generation of polyclonal responses recognizing tumor cells endogenously expressing the specific peptides. The responses generated are robust, antigen-specific and reproducible if the peptide epitope is a defined immunogen. This artificial antigen expression system can be adapted to treat most cancers in a significant majority of the population.

Cell therapy method for the treatment of tumors

T cell responses are often diminished in humans with a compromised immune system. We have developed a method to isolate, stimulate and expand na&#xef;ve cytotoxic T lymphocyte precursors (CTLp) to antigen-specific effectors, capable of lysing tumor cells in vivo. This ex vivo protocol produces fully functional effectors. Artificial antigen presenting cells (AAPCs;) transfected with human HLA class I and defined accessory molecules, are used to stimulate CDT cells from both normal donors and cancer patients. The class I molecules expressed to a high density on the surface of thecells are empty, allowing for efficient loading of multiple peptides that results in the generation of polyclonal responses recognizing tumor cells endogenously expressing the specific peptides. The responses generated are robust, antigen-specific and reproducible if the peptide epitope is a defined immunogen. This artificial antigen expression system can be adapted to treat most cancers in a significant majority of the population.

Methods of processing inactivated artificial antigen presenting cells (aAPCs) and artificial antigen presenting cells with specificity for selected antigenic peptides are described, including their generation and use in cell therapy compositions comprising activated cytotoxic T lymphocytes. Inactivated aAPCs are advantageously generated through crosslinking, such as via a photoreaction involving a psoralen derivative and UVA irradiation.

Preparation of inactivated artificial antigen presenting cells and their use in cell therapies

This invention provides hybridoma cell lines producing monoclonal antibodies which inhibit CD14 mediated cell activation. Monoclonal antibodies produced by these cell lines also are provided. The antibodies are useful for the detection of the presence of cell surface and soluble CD14 in a sample. Chimeric and CDR grafted antibodies generated from the above monoclonal antibodies are further provided. Pharmaceutical compositions containing the above biological compositions are provided. These are useful to treat and prevent disorders with CD14 mediated cell activation, such as sepsis.

Hybrid cells producing monoclonal anti-CD14 antibodies

This invention provides a method of isolating CD8cells which employs an antibody which specifically binds to CD8 molecules present on the surface of CD8cells but does not activate the CD8cells once bound. This invention also provides related hybridoma cell lines, monoclonal antibodies, antigenic polypeptides, isolated CD8cells, and kits.

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The present invention concerns a method of treating LBP-mediated LPS-induced myeloid cell activation comprising administering a therapeutically effective amount of an anti-LBP monoclonal antibody molecule. A therapeutic composition comprising anti-LBP antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Monoclonal antibodies immunoreactive with lipopolysaccharide binding protein (LBP) and methods of their use

The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrices can be used to activate CD8 T-cells to produce cytokines and become cytotoxic.

Antigen presenting system and methods for activation of T-cells

This invention provides a method of isolating CD8 cells which employs an antibody which specifically binds to CD8 molecules present on the surface of CD8 cells but does not activate the CD8 cells once bound. This invention also provides related hybridoma cell lines, monoclonal antibodies, antigenic polypeptides, isolated CD8 cells, and kits.

Method of isolating CD8&plus; cells, and related hybridoma cells antibodies and polypeptides

Materials and methods of activating T lymphocytes with specificity for particular antigenic peptides are described, as well as the use of activated T lymphocytes in vitro for the treatment of a variety of disease conditions. In particular, a synthetic antigen presenting matrix for activating T lymphocytes to a specific peptide is described.

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San Diego, CA, United States of America

Didier J Leturcq