MedImmune and Micromet have provided details on a novel drug molecule that targets a tyrosine kinase receptor that is frequently overexpressed on solid tumours and provides the opportunity to develop an anti-cancer therapeutic, which may minimise potential side effects for patients.
The drug molecules in question, BiTE, are part of a novel class of antibody derivatives that may have the potential to selectively direct and activate an individual's own immune system to act against cancer cells.
This action is believed to occur as a result of the molecule's stimulation of T cells (a very potent type of white blood cell) to target and destroy cancer cells that over-express a specific antigen.
BiTE molecules are the result of a successful collaboration between biotechnology company MedImmune and Micromet, a biopharmaceutical company. Their targeting of the tyrosine kinase receptor EphA2, represents a novel target for the development of molecular therapeutics for the imaging and treatment of patients with cancer.
New therapies are clearly needed because, despite the standard treatment of surgically removing the tumour and treating the patient with chemotherapy and radiation, survival has increased only slightly over the past 30 years."
Previous research has shown EphA2 may also show promise as a target for other types of cancer.
It has been shown to be present at high levels in several other tumours, such as pancreas, colon and breast.
Additionally other researchers have shown that EphA2 is a potential target for a glioblastoma vaccine that could potentially prevent recurrences of the tumours.
In in vitro studies, the BiTE molecule, bscEphA2xCD3 was observed to kill tumour cells at low nanogram/ml concentrations, which is considerably below dose levels currently required by classical monoclonal antibody-based therapies.
Tumour cell lysis approached 100 percent even at low ratios of effector T cells to target cells.
In mice, the BiTE compound redirected unstimulated human T cells to inhibit transplanted human tumor outgrowth without the apparent need for co-stimulation of T cells.
Of note, videomicroscopy showed that bscEphA2xCD3 triggered T cells to attack single tumour cells overexpressing EphA2 but spared normal cells where the tyrosine kinase is sequestered within intercellular boundaries.
"These results further support the common and unique characteristics of BiTE and suggest that BiTE molecules may make for a novel platform of antibody-based therapeutics," said Patrick Baeuerle, Micromet's CSO.
"Our findings suggest that the form of the EphA2 target, which may be only accessible on tumor cells, may provide the basis for selective tumour cell lysis by an EphA2 specific BiTE."
Under the terms of the companies' collaboration agreement, MedImmune holds the rights to bscEphA2xCD3. Micromet is entitled to receive milestones and royalties in case of successful development and commercialisation of the compound and has the option to receive co-promotion rights in Europe.
Both companies presented their data earlier this week at the National Cancer Institute's 14th SPORE Investigators' Workshop.