MedImmune, Micromet: BiTE may offer anticancer therapeutic with fewer side effects

By E. Janene Geiss

Philadelphia, July 21 - MedImmune, Inc. and Micromet, Inc. said Friday that recent data suggest bscEphA2xCD3, or BiTE, which targets the tyrosine kinase receptor EpjA2 frequently overexpressed on solid tumors, may provide the opportunity to develop an anticancer therapeutic, which may minimize potential side effects for patients.

The compound has been generated in the context of the companies' research collaboration for the development of new therapeutics based on Micromet's BiTE technology, according to a company news release.

The data was presented earlier this week at the National Cancer Institute's 14th Spore Investigators' Workshop.

In in vitro studies, bscEphA2xCD3 was observed to kill tumor cells at low nanogram/ml concentrations, which is considerably below dose levels currently required by classical monoclonal antibody-based therapies, officials said.

Tumor cell lysis approached 100% 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, officials said.

Of note, videomicroscopy showed that bscEphA2xCD3 triggered T cells to attack single tumor cells overexpressing EphA2, but spared normal cells where the tyrosine kinase is sequestered within intercellular boundaries.

BiTE molecules 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.

"These results ... suggest that BiTE molecules may make for a novel platform of antibody-based therapeutics," Patrick Baeuerle, Micromet's chief scientific officer, said in the release.

The findings also suggest the form of the EphA2 target, which may be only accessible on tumor cells, may provide the basis for selective tumor cell lysis by an EphA2 specific BiTE, Baeuerle added.

Under terms of the collaboration, MedImmune said it holds the rights to bscEphA2xCD3. Micromet said it is entitled to receive milestones and royalties in case of successful development and commercialization of the compound and has the option to receive co-promotion rights in Europe.

Under a separate arrangement, Micromet and MedImmune said they collaborate on the development of MT103/MEDI-538, a BiTE molecule being developed to treat B-cell non-Hodgkin's lymphoma.

MT103/MEDI-538 specifically targets the CD19 antigen present on B cells, but not on other types of blood cells or healthy tissues.

MedImmune is a Gaithersburg, Md., biopharmaceutical company.

Micromet is a Carlsbad, Calif., biopharmaceutical company.

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