Tolerx Presents Preclinical Data on Novel T-cell Modulator, TRX518, for Antitumor Immune Response at Federation of Clinical Immunology Societies Scientific Meeting
Anti-GITR Combined with Chemotherapy Achieved Tumor Reduction and Survival Benefit in Animal Model
CAMBRIDGE, Mass., June 25 /PRNewswire/ -- Tolerx, Inc., a
biopharmaceutical company developing novel therapies to treat
autoimmune diseases and cancer by modulating T cell activity,
presented results from preclinical studies with TRX518, an
early-stage agent Tolerx is developing as a treatment for cancer.
TRX518 is a monoclonal antibody to glucocorticoid-induced tumor
necrosis factor receptor (GITR) and is designed to enhance the
immune system's ability to attack tumors by activating and
rendering T effector cells resistant to T regulatory cell
suppression. Anti-GITR agents have been identified by the National
Cancer Institute as having high potential for treating cancer. The
preclinical data were presented and recognized as a distinguished
abstract at the annual meeting of the Federation of Clinical
Immunology Societies in Boston, Massachusetts.
The data included in the presentation demonstrated that a murine
analog of TRX518, which is an anti-GITR antibody, resulted in
pronounced and durable immune responses to several antigens in
mice. These data also showed that the TRX518 analog, when combined
with gemcitabine, a standard chemotherapeutic, significantly
reduced tumor burden (p<0.001) and prolonged survival
(p<0.001) in the mouse model when compared with gemcitabine
alone. In particular, of the mice treated with the combination
therapy, 65% had a complete remission. Similar findings were
observed when the TRX518 analog was combined with cyclophosphamide.
The humanized monoclonal antibody, TRX518, blocked the interaction
of GITR with its ligand, enhanced the cytotoxicity of human natural
killer cells, downmodulated GITR on peripheral blood lympocytes,
did not induce appreciable cytokine release, and was well tolerated
and safe at high doses in non-human primates.
"We are highly encouraged by the preclinical results with
anti-GITR immunotherapy. This approach appears to induce unique
mechanisms for augmenting antitumor immune responses and holds
promise for treating malignancies in man," said Louis Vaickus, MD,
Chief Medical Officer at Tolerx. "In a murine model of established
colon cancer, the results, especially the complete remissions, were
striking and these findings represent preclinical proof of concept
for TRX518."
About TRX518
TRX518 is a targeted T-cell immunomodulator that binds to the
glucocorticoid-induced tumor necrosis factor receptor (GITR) found
on multiple types of T cells and other immune cells. Activated GITR
plays a role in directing the antitumor immune response via
activating tumor-antigen-specific T effector cells, as well as
abrogating the suppression induced by inappropriately activated T
regulatory cells. In preclinical studies, TRX518 achieved its
targeted effect without compromising normal immune function and
preclinical models suggest TRX518 may have a reduced risk of
causing the serious inflammatory side effects that can result from
cytokine release.
About Tolerx
Tolerx, Inc., a world leader in the understanding of T cell
function, is developing novel therapies intended to treat
autoimmune diseases, diabetes, and cancer by specifically
modulating T cell activity. The company's pipeline includes its
lead candidate, otelixizumab, a targeted T cell immunomodulator in
Phase 3 development for the treatment of type 1 diabetes that is
partnered with GlaxoSmithKline. TRX1, a Phase 1 candidate, is a
nonlytic anti-CD4 antibody that is being developed for the
treatment of aberrant or untoward immune responses. The company
also has three preclinical candidates, TRX518, TRX585, and TRX385,
which enhance immune responses and as such are being evaluated for
potential benefit in the treatment of cancer and chronic
infections. Tolerx is a privately held company headquartered in
Cambridge, MA USA. For more information, please visit
www.tolerx.com.
Source: Tolerx, Inc.
CONTACT: Kathryn Morris, The Yates Network,
+1-845-635-9828,
kathryn@theyatesnetwork.com
Web Site: http://www.tolerx.com/
Posted: June 2010
