Micromet's BiTE(R) Antibodies Reveal Unique Mode of Action
BiTE antibodies are designed to transiently connect cytotoxic T cells withcancer cells leading to a tightly controlled and serial elimination of cancercells. In this process, cytotoxic T cells are activated, which causes them toproliferate, recharge their toxins and increase their adhesiveness.
The two new studies have shown that BiTE antibodies activate T cells onlywhen cancer cells are present, but not when they are given to T cells in theabsence of cancer cells. The studies have also shown that initial cytokinerelease by activated T cells is not required for elimination of cancer cells,and that anti-inflammatory steroid hormones can efficiently quench the initialcytokine release by BiTE-activated T cells without reducing their capacity tokill cancer cells.
"The highly conditional, target cell-dependent activation of killer Tcells by our BiTE antibodies is a very important safety feature in patients,"commented Patrick Baeuerle, Micromet's Chief Scientific Officer. "Unlike otherT cell-activating agents, BiTE antibodies activate T cells in a highlycontrolled fashion that is intimately linked to the desired therapeuticactivity."
"We have observed depletion of circulating B lymphoma cells and haveconfirmed partial and complete responses in the clinical trials with MT103. Atthe same time, only very low systemic cytokine levels, if any, were detected,"commented Carsten Reinhardt, Micromet's Chief Medical Officer. "The sideeffect profile of MT103 seen in the ongoing phase 1 study is consistent withthe conditional T cell activation observed in the newly published studies."
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 therapeuticapproach to cancer therapy. BiTE antibodies have been shown to induce animmunological synapse between a T cell and a tumor cell in the same manner asobserved during physiological T cell attacks. These cytolytic synapses enablethe delivery of cytotoxic proteins from T cells into tumor cells, ultimatelyinducing a self-destruction process in the tumor cell referred to asapoptosis, or programmed cell death. In the presence of BiTE antibodies, Tcells have been demonstrated to serially eliminate tumor cells, which explainsthe activity of BiTE antibodies at very low concentrations and at very lowratios of T cells to target cells. Through the process of killing cancercells, T cells proliferate, which leads to an increased number of T cells atthe site of attack.
Several antibodies in Micromet's product pipeline are BiTE antibodies andhave been generated based on Micromet's proprietary BiTE product developmentplatform. The most advanced BiTE antibody is MT103 (MEDI-538), targetingCD19, and has provided proof-of-concept in an ongoing phase 1 clinical studyin advanced non-Hodgkin's lymphoma patients. Three other BiTE antibodies,targeting EpCAM (CD326), CEA and MCSP, are in pre-clinical development.
About Micromet, Inc. (www.micromet-inc.com)
Micromet, Inc. is a biopharmaceutical company developing novel,proprietary antibodies for the treatment of cancer, inflammation andautoimmune diseases. Three of its antibodies are in clinical development.MT103 (MEDI-538), the first antibody developed utilizing the BiTE(R)technology platform in Micromet's product pipeline, is being evaluated in aphase 2 clinical trial for the treatment of patients with acute ly
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