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The art of the cell
LOS ANGELES—ImmunoCellular Therapeutics, a clinical-stage company that is developing immune-based therapies for the treatment of brain and other cancer, has entered an option agreement with the University of Texas M.D. Anderson Cancer Center relating to an immunotherapy targeting cancer stem cells (CSCs).
The agreement bolsters ImmunoCellular's portfolio of technologies targeting CSCs. This portfolio already features several promising therapies, including ICT-107, a dendritic cell based immunotherapy that recently completed a Phase I study, and ICT-121, an off-the-shelf peptide vaccine that targets a protein marker called CD133 that is overexpressed on cancer stem cells. IND filings for FDA approval to begin human clinical trials for ICT-121 are expected for brain cancer during the first quarter of 2010 and for pancreatic cancer during the third quarter of the year.
According to Manish Singh, president and CEO of ImmunoCellular, the deal gives the company worldwide, exclusive rights to the technologies when the option agreement ends. No financial terms have been disclosed due to confidentiality requirements from both sides, Singh adds.
The technology being optioned from M.D. Anderson is an immunotherapy targeting cancer stem cells using abnormal Notch and Numb pathways, two mechanisms implicated in many common solid tumors including breast, colon and ovarian cancers. The therapy was developed at M.D. Anderson by Dr. Constantin G. Ioannides and Satoko Matsueda. Ioannides is also credited, along with others, with the development of the E75 peptide targeting Her-2/neu, which has been tested in a Phase II study to prevent breast cancer recurrence.
Malfunctioning of the notch pathway is a common phenomenon on several cancers marked by an overexpression of notch protein on cancer stem cells. The notch pathway is a signaling mechanism that regulates stem cells and in cases of cancer it acts as an oncogene that promotes the growth of tumors.
A number of cancers such as leukemia, lymphoma, breast cancer, lung cancer and brain cancer are known to have aberrant notch signaling leading to cells with greater migratory facilities which promotes metastasis. Research indicates that cytotoxic T cells induced by these peptides preferentially target cancer stem cells derived from breast cancer, ovarian cancer and pancreatic cancer; expression of these peptides has been demonstrated on clinical samples from ovarian cancer patients.
"We plan to use this to develop novel immunotherapy products to target breast cancer and ovarian cancer initially. These may also be applicable to other cancers due to shared commonalities between various cancers," Singh says. "We plan to conduct preclinical work for the next twelve months to demonstrate utility of these peptides in several cancer models."
According to Singh, smlecting the M.D. Anderson Cancer Center as a partner wasn't a difficult decision.
"They have unique technologies developed to target notch and numb pathways, which we had earlier identified as one of the major pathways for our product development efforts," Singh says. "This latest addition to our portfolio of CSC targeting therapies should serve to further increase our ability to specifically identify and destroy these important tumor building blocks by targeting additional pathways that were not addressed by our current portfolio. By acquiring rights to this previously unaddressed pathway, we are now well positioned to continue development of a therapy that will enhance our ability to target these important cells, which we believe may lead to more effective and better tolerated treatments that are capable of targeting a number of different tumor types."
Singh says a successful IND in 2011 will be the main goal of the collaboration.
ImmunoCellular also has a research and license option deal with Roche for one of its mAbs for the diagnosis and treatment of ovarian cancer and multiple myeloma. The company stands to earn up to $32 million in licensing and milestone payments plus royalties if Roche exercises its option and commercializes the technology for multiple indications.
ImmunoCellular is also in preclinical development of another monoclonal antibody product candidate for the treatment of small-cell lung cancer and pancreatic cancer, and is also evaluating its platform technology for monoclonal antibody discovery using differential immunization for diagnosing and treating multiple types of cancer.
While Roche and Merck develop early clinical-stage gamma-secretase inhibitors that block notch signaling, ImmunoCellular is targeting cancer stem cells that express aberrant notch peptides by educating the immune system to recognize and attack these cells.
They aren't the only companies working in this area. OncoMed and GlaxoSmithKline formed a strategic alliance in late 2007 that included a cancer stem cell monoclonal antibody, OMP-21M18, that is currently in Phase I clinical development and works by blocking a notch receptor signaling component.