Earlier today, Stemline Therapeutics, Inc., a clinical stage biopharmaceutical company developing novel oncology compounds that target cancer stem cells (CSCs), announced that it holds the license from the University of Pittsburgh for the exclusive worldwide rights to a clinically active oncology vaccine directed to multiple defined targets on tumor bulk and CSCs.

Developed by Hideho Okada, M.D, PhD, Associate Professor of Neurological Surgery and his colleagues at University of Pittsburgh, the vaccine demonstrated safety, tolerability, and anti-tumor activity as a single agent in a Phase I, National Institutes of Health-funded study conducted at the university in 22 participants with recurrent high-grade glioma.

Immune response
This vaccine approach produces an immune response against gliomas, the lethal, difficult-to-treat primary tumors that aggressively invade the folds and creases of the brain, and is based on four tumor antigens commonly found on the surface of gliomas. Rather than taking antigens from a particular patient to evoke an immune response, Okada?s technique uses a more general collection of antigens. Because gliomas grow quickly, the time needed to isolate patient-specific peptides would allow the disease to progress to the point at which treatment would be futile. The vaccine is based on a multi-antigen approach, in which four different peptides are modified to look more ‘dangerous’ to the immune system, potentially eliciting a stronger immune response.

Standard treatment
Cancer Stem Cells comprise a unique subpopulation of neoplastic cells within tumors that is highly tumorigenic and relatively resistant to standard therapy. While conventional anti-cancer treatments such as chemotherapy and radiation, can often transiently shrink tumors by targeting tumor bulk, these therapies fail to target and kill CSCs leading to treatment failure, relapse, and ultimately death. In order to overcome these traditional pitfalls, Stemline is developing novel therapeutics that target and eradicate CSCs.

Study Findings
According to Dr. Okada’s research findings, published recently in the Journal of Clinical Oncology, the most common grade 1-2 adverse events (AEs) were injection site reactions and fatigue. There were no grade 3 or 4 AEs. The vaccine elicited immune responses in 81% of evaluable patients. A high rate of overall response and disease stabilization was observed in this heavily pre-treated population, including 46% (6/13) in glioblastoma (GBM), and 67% (6/9) in anaplastic glioma (AG). Notably, there was one durable complete response (CR) of greater than 12 months in a 1st salvage GBM patient, and one partial response (PR) of 7 months duration in a 2nd salvage GBM patient. In both cases, the vaccine induced tumor shrinkage as determined by MRI according to standard RECIST (Response Evaluation Criteria In Solid Tumors) criteria. A survival improvement over historical data was also observed in both the recurrent GBM and AG populations. The vaccine and its derivatives are being developed by Stemline under the name SL-701 as both an ‘off-the-shelf’ peptide vaccine and a dendritic cell (DC) vaccine.

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Tom Cirrito, PhD, Director of Operations at Stemline noted, “We became interested in University of Pittsburgh’s vaccine because of its dual targeting of both tumor bulk and cancer stem cells. In addition, by virtue of its targeting of multiple defined epitopes, we are able to determine the specificity and magnitude of the immune response in patients. Importantly, we have also observed reductions in tumor size as well as improvements in survival, consistent with the drug’s mechanism of action.”

Stemline’s CEO, Ivan Bergstein, MD, commented on the in-licensing, “We are excited to add another clinical stage therapeutic to our pipeline. With this acquisition, we now have two clinical programs that have demonstrated complete responses and a survival benefit in heavily pre-treated populations. We are committed to a development strategy that rapidly advances these programs through the regulatory process toward commercialization.”

The vaccine that is the basis of the Company’s second clinical program has completed a Phase I/II trial at University of Pittsburgh in adult patients with recurrent malignant glioma (brain cancer) where it has demonstrated single agent activity including a durable CR and an OS benefit. This cancer vaccine, now being further developed by Stemline as SL-701, is poised for Phase II/III trials in patients with recurrent malignant glioma.

For more information:
Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011 Jan 20;29(3):330-6. Epub 2010 Dec 13.

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