Northwest Biotherapeutics, Inc.

Northwest Hospital

Anil Sehgal

Alton L Boynton

Gerald P Murphy

Bridgette Murphy

The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.

Therapeutic and diagnostic applications based on the role of the CXCR-4 gene in tumorigenesis

The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicant's surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.

The present invention relates to the identification of a novel role of Nr-CAM in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of Nr-CAM in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for Nr-CAM. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of Nr-CAM gene expression or the inhibition of Nr-CAM activity in transformed cells reverses the transformed phenotype.

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The present invention relates to the discovery, identification and characterization of a novel tumor suppressor gene C4-2. The invention encompasses nucleotide sequences of the C4-2 gene and amino acid sequences of its encoded protein product(s), as well as derivatives and analogs thereof. The invention also encompasses the production of C4-2 proteins and antibodies. The invention further encompasses therapeutic compositions and methods of diagnosis and therapy.

Nucleotide and amino acid sequences of C4-2, a tumor suppressor gene,

Nucleotide sequences of D2-2 genes (human D2-2 and D2-2 homologs of other species), and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof are disclosed. Nucleic acids hybridizable to or complementary to the nucleotide sequences are also disclosed. D2-2 is a gene expressed at high levels in glioblastoma multiforme tissue as well as certain other forms of tumors and cancers. Therapeutic and diagnostic methods and compositions based on D2-2 proteins fragments and analogs, anti-D2-2 antibodies and nucleic acids for treatment of disorders of overproliferation (e.g., tumors, cancer and hyperproliferative disorders are disclosed.

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Dublin, CA, United States of America

Anil Sehgal