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The inventors have developed methods and reagents for the detection of bone sialoprotein (BSP) in biological samples. The technology relates to the disruption of a serum complex that masks the majority of BSP from established detection systems. Furthermore, there is evidence that there may be a more acidic form of BSP secreted not by normal bone, but only by tumors. Detection of BSP in serum may be a good marker of various bone diseases and a variety of cancers including breast, prostate, lung, and thyroid.

This application describes a composition and method for treating inflammatory bowel disease or other autoimmune diseases. The composition utilizes a vector which contains a first promoter which controls the expression of a regulatory transcription factor and a second inducible promoter which controls the expression of the gene of interest. The preferred gene of interest encodes an isoform of TGF-beta such as TGF-beta₁ or TGF-beta₃. The isoform of TGF-beta does not have to be hTGF-beta and can be a latent or active isoform of TGF-beta.

Cytokines exert their respective biochemical and physiological effects by binding to specific receptor molecules, which then stimulate signal transduction pathways. Interleukin-21 (IL-21) is a type I cytokine whose receptor is expressed on T, B, and NK cells.

Approximately 30,000 patients are diagnosed with renal cell carcinoma (RCC) each year in the United States, and an estimated 12,000 patients die of this disease. Most patients are diagnosed with advanced local disease or metastatic disease. Metastatic RCC carries a poor prognosis with median survivals in the range of 10-12 months. Drugs that inhibit VEGF receptor tyrosine kinases such as Sorafenib and Sunitinib have recently been approved by the FDA to treat metastatic RCC.

Immuno-therapy has taken a lead among the new cancer therapeutic approaches. It is one of the most promising new therapeutic approaches that exploit the innate immune mechanism of an individual to fight against a certain disease.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris.

This technology identifies twenty five (25) new alternatively spliced transcripts of the BORIS gene. The transcripts lead to the expression of seventeen different protein isoforms with variable N- and C-termini encoded by BORIS gene locus. Differential expression levels of BORIS isoforms were observed in different cancers. While some BORIS alternative splice variants were expressed at different levels in all types of cancers, other expressed forms are specific to particular cancer(s).

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts.

The invention concerns immunotoxins and methods of making the immunotoxins. Targeting of the immunotoxins occurs via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. As a result, the immunotoxin can be used to treat autoimmune disease, malignant T cell-related cancers, and graft-versus-host disease.

The ubiquitin-proteasome system has recently been recognized to play a central role in tumor biology. Bortezomib, an inhibitor of the chymotrypsin-like activity of the proteasome, has clinical activity in a variety of hematologic malignancies and is FDA approved for use in Multiple Myeloma and Mantle Cell Lymphoma.