Dana-Farber-Cancer Institute Inc.

Institut National De La Sante Et De La Recherche Medicale

Boston University

Joachim L Schultze

Lee M Nadler

Gordon James Freeman

Vassiliki A Boussiotis

John G Gribben

Robert H Vonderheide

Kathryn T Hall

Armand Bensussan

Laurence Boumsell

David H Sherr

William C Hahn

Britta Maecker

Michael Bergwelt-Baildon

The invention provides methods for conducting cancer immunotherapy and diagnosis using universal tumor associated antigens, such as the telomerase catalytic subunit (hTERT), and methods for identifying and characterizing universal tumor associated antigens.

Cancer immunotherapy and diagnosis using universal tumor associated antigens, including hTERT

Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Nucleic acids encoding CD100 molecules

The invention provides methods for conducting cancer immunotherapy and diagnosis using cytochrome P450 1B1 and peptide fragments thereof.

Cancer immunotherapy and diagnosis using cytochrome P450 1B1

We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1&#xd7;10to 1&#xd7;10fold in 2 weeks or 1&#xd7;10to 1&#xd7;10fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4CD45RA, CD4CD45RO, and CD8T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF&#x3b2;.

Methods of inducing a T cell mediated immune response by administering antigen presenting B cells

CD100 antigen and uses therefor

We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1&times;10 to 1&times;10 fold in 2 weeks or 1&times;10 to 1&times;10 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4 CD45RA , CD4 CD45RO , and CD8 T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF&bgr;.

Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin

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Brookline, MA, United States of America

Joachim L Schultze