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Preclinical Study Published In Cancer Research Demonstrates Anti-Tumor Activity Of Micromet's BiTE Antibody At Well Tolerated Doses
Micromet, Inc.
(Nasdaq: MITI), a biopharmaceutical company developing novel, proprietary
antibodies for the treatment of cancer, inflammation and autoimmune
diseases, announced the publication of a new preclinical study in
Cancer Research(1) demonstrating that efficacious doses of a BiTE(R)
antibody targeting epithelial cell adhesion molecule (EpCAM or CD326) are
well tolerated in two mouse cancer models. BiTE antibodies join cytotoxic T
cells with cancer cells for a tightly controlled elimination of cancer
cells.
EpCAM is one of the most frequently and highly expressed
tumor-associated antigens and is found on the majority of colon, lung,
breast, prostate, ovarian, gastric, pancreas and on cancer stem cells. Like
other tumor- associated antigens used as targets for antibody-based
therapeutics, EpCAM is expressed on certain normal tissues. In order to
assess the safety profile of an EpCAM-specific BiTE antibody, Micromet's
researcher constructed a murine- specific BiTE antibody, called muS110,
that is similar to the human-specific BiTE antibody MT110 with respect to
structure, binding strength, efficacy and epitope recognition on EpCAM.
EpCAM was found to be similarly expressed by mice and humans.
Low doses of muS110 that prevented growth of orthotopic breast cancer
and formation of lung metastases in mice were well tolerated. Treatment
with MuS110 did not lead to any damage of EpCAM-expressing normal tissues
at any dose studied. This indicates that the EpCAM-specific BiTE antibody
did recognize EpCAM on tumor cells but not on cells of normal tissues.
"We were pleased to see that an EpCAM-specific BiTE antibody showed
anti- tumor activities at well tolerated doses," commented Patrick
Baeuerle, Micromet's Chief Scientific Officer. "It appears that normal
tissues expressing EpCAM are not affected by our BiTE antibody. We are now
looking forward to testing the safety and clinical activity of MT110, a
human EpCAM- specific BiTE antibody, in a phase 1 clinical trial in the
near future."
About BiTE(R) Antibodies
BiTE(R) antibodies are designed to direct the body's cytotoxic, or
cell- destroying, T cells against tumor cells, and represent a new
therapeutic approach to cancer therapy. BiTE antibodies have been shown to
induce an immunological synapse between a T cell and a tumor cell in the
same manner as observed during physiological T cell attacks. These
cytolytic synapses enable the delivery of cytotoxic proteins from T cells
into tumor cells, ultimately inducing a self-destruction process in the
tumor cell referred to as apoptosis, or programmed cell death. In the
presence of BiTE antibodies, T cells have been demonstrated to serially
eliminate tumor cells, which explains the activity of BiTE antibodies at
very low concentrations and at very low ratios of T cells to target cells.
Through the process of killing cancer cells, T cells proliferate, which
leads to an increased number of T cells at the site of attack.
Several antibodies in Micromet's product pipeline are BiTE antibodies
and have been generated based on Micromet's proprietary BiTE antibody
development platform. The most advanced BiTE antibody is MT103 (MEDI-538),
targeting CD19, and has provided proof-of-concept for the platform in an
ongoing phase 1 clinical study in advanced non-Hodgkin's lymphoma patients.
Three other BiTE antibodies, targeting EpCAM (CD326), CEA and MCSP, are in
pre-clinical development.
About Micromet, Inc.
BiTE is a registered trademark of Micromet. Micromet, Inc. is a
biopharmaceutical company developing novel, proprietary antibodies for the
treatment of cancer, inflammation and autoimmune diseases. Three of its
antibodies are in clinical development. MT103 (MEDI-538), the first
antibody developed utilizing the BiTE(R) antibody technology platform in
Micromet's product pipeline, is being evaluated in a phase 2 clinical trial
for the treatment of patients with acute lymphoblastic leukemia and a phase
1 clinical trial for the treatment of patients with non-Hodgkin's lymphoma.
BiTE antibodies represent a new class of antibodies that activate a
patient's own cytotoxic T cells to eliminate cancer cells. Micromet is
developing MT103 in collaboration with MedImmune, a subsidiary of
AstraZeneca plc. The second clinical stage antibody is adecatumumab
(MT201), a human monoclonal antibody targeting EpCAM expressing tumors.
Adecatumumab is being developed by Micromet in collaboration with Merck
Serono in a phase 1b clinical trial evaluating MT201 in combination with
docetaxel for the treatment of patients with metastatic breast cancer. The
third clinical stage antibody is MT293 (formerly D93), also known as
TRC093, a first-in-class humanized monoclonal antibody that inhibits
angiogenesis and tumor cell growth by binding cleaved collagen. MT293,
which is currently being tested in a phase 1 clinical trial, is licensed to
TRACON Pharmaceuticals, Inc. and is being developed for the treatment of
patients with cancer and age-related macular degeneration. In addition,
Micromet has established a collaboration with Nycomed for the development
and commercialization of MT203, Micromet's human antibody neutralizing the
activity of granulocyte/ macrophage colony stimulating factor (GM-CSF),
which has potential applications in the treatment of various inflammatory
and autoimmune diseases, such as rheumatoid arthritis, psoriasis, or
multiple sclerosis.
Forward-Looking Statements
This release contains certain forward-looking statements that involve
risks and uncertainties that could cause actual results to be materially
different from historical results or from any future results expressed or
implied by such forward-looking statements. Factors that may cause actual
results to differ materially from any future results expressed or implied
by any forward-looking statements include the risk that product candidates
that appeared promising in early research, preclinical studies or clinical
trials do not demonstrate safety and/or efficacy in subsequent clinical
trials, the risk that encouraging results from early research, preclinical
studies or clinical trials may not be confirmed upon further analysis of
the detailed results of such research, preclinical study or clinical trial,
the risk that additional information relating to the safety, efficacy or
tolerability of our product candidates may be discovered upon further
analysis of preclinical or clinical trial data, the risk that we or our
collaborators will not obtain approval to market our product candidates,
the risks associated with reliance on outside financing to meet capital
requirements, and the risks associated with reliance on collaborators,
including MedImmune, Merck Serono, TRACON and Nycomed, for the funding or
conduct of further development and commercialization activities relating to
our product candidates. You are urged to consider statements that include
the words "ongoing," "may," "will," "would," "could," "should," "believes,"
"estimates," "projects," "potential," "expects," "suggests," "plans,"
"anticipates," "intends," "continues," "forecast," "designed," "goal," or
the negative of those words or other comparable words to be uncertain and
forward-looking. These factors and others are more fully discussed in our
periodic reports and other filings with the SEC.
Any forward-looking statements are made pursuant to Section 27A of the
Securities Act of 1933, as amended, and Section 21E of the Securities
Exchange Act of 1934, as amended, and, as such, speak only as of the date
made. Micromet, Inc. undertakes no obligation to publicly update any
forward-looking statements, whether as a result of new information, future
events or otherwise.
(1) Cancer Res 2008;68(1):143-51
Micromet, Inc
http://www.micromet-inc.com
Preclinice de studiu publicat în Cancer Research demonstreazã Anti-tumoare activitatea Micromet lui Musca anticorpi La bine toleratã Dozele - Preclinical Study Published In Cancer Research Demonstrates Anti-Tumor Activity Of Micromet's BiTE Antibody At Well Tolerated Doses - articole medicale engleza - startsanatate