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Needham, MA, United States

Williams M.D.,515 Holcombe Blvd. | Esmaeli B.,Section of Ophthalmology | Soheili A.,Section of Ophthalmology | Simantov R.,Curagen Corporation | And 3 more authors.
Melanoma Research | Year: 2010

Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in≥50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rose A.A.N.,McGill University | Grosset A.-A.,University of Montreal | Grosset A.-A.,INRS Institute Armand Frappier | Dong Z.,McGill University | And 9 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Although the murine orthologue of glycoprotein nonmetastatic B (GPNMB), Osteoactivin, promotes breast cancer metastasis in an in vivo mouse model, its importance in human breast cancer is unknown. We have examined the significance of GPNMB expression as a prognostic indicator of recurrence and assessed its potential as a novel therapeutic target in breast cancer. Experimental Design: The clinical significance of GPNMB expression in breast cancer was addressed by analyzing GPNMB levels in several published gene expression data sets and two independent tissue microarrays derived from human breast tumors. GPNMB-expressing human breast cancer cell lines were further used to validate a toxin-conjugated anti-GPNMB antibody as a novel therapeutic agent. Results: GPNMB expression correlates with shorter recurrence times and reduced overall survival of breast cancer patients. Epithelial-specific GPNMB staining is an independent prognostic indicator for breast cancer recurrence. GPNMB is highly expressed in basal and triple-negative breast cancers and is associated with increased risk of recurrence within this subtype. GPNMB expression confers a more migratory and invasive phenotype on breast cancer cells and sensitizes them to killing by CDX-011 (glembatumumab vedotin), a GPNMB-targeted antibody-drug conjugate. Conclusions: GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of poor outcome in patients with breast cancer. CDX-011 (glembatumumab vedotin) is a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks targeted-therapy options. ©2010 AACR.

Topo Target UK Ltd and Curagen Corporation | Date: 2014-11-26

The present invention pertains to a method for treating cancer, such as lung cancer, multiple myeloma, lymphoma, and epithelial ovarian cancer, comprising the administration to a patient in need thereof a first amount or dose of a histone deacetylase (HDAC) inhibitor, such as PXD-101, and a second amount or dose of another chemotherapeutic agent, such as dexamethasone or 5-fluorouracil, or an epidermal growth factor receptor (EGFR) inhibitor, such as Tarceva, wherein the first and second amounts or doses together comprise a therapeutically effective amount.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 702.04K | Year: 1995

Improving the speed and efficiency of DNA sequencing methods is essential to the success of the Human Genome Program and to the success of many biotechnology companies such as CuraGen. DNA sequencing remains the rate determining step in much of genetic research. Our goal (and the subject of this proposal) is to dramatically increase the speed and efficiency of gel electrophoresis sequencing using fluorescently tagged DNA. We will investigate the upper throughput bounds of this method by (1) increasing optical format and efficiency, (2) massively increasing the lane density and, hence, the number of samples per run, and (3) improving data handling efficiency through software and dye coding strategies. Sensitivity and throughput increases of 20 fold each may be realized through implementation of optical improvements and a new separation technique. The optical spectroscopy, computation, mathematics, engineering and molecular biology backgrounds present at CuraGen combine with a strong consulting base to put us in a unique position to conceive and carry out this effort. If successful, the instrumental advances achieved in Phase I will be developed into a Phase II prototype. The Phase II prototype will be capable of accepting standard 96 well microtitration plates directly and have an immense commercial advantage over existing systems.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 88.61K | Year: 1996


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