CD3 Antagonists

The present Competitive Intelligence Report about CD3 Antagonists provides a competitor evaluation in the field of approved and investigational antibodies and other biologic constructs targeting CD3 for treatment of autoimmune diseases and cancer as of March 2009.

CD3 is a T lymphocyte receptor involved in normal cell signaling. Antagonists of CD3 are thought to work by blocking the function of T effector cells that attack the body's tissues and cause autoimmune disease while inducing a subset of T cells known as T regulatory cells. It is thought that the T regulatory cells may protect against T effector cell damage well after the drug has been eliminated from the body. CD3 antagonist antibodies are currently being evaluated in number of inflammatory or autoimmune diseases, especially in type 1 diabetes but also in transplantation, psoriasis, Crohn's disease and rheumatoid arthritis. The most advanced programs are in phase III.

CD3 is also utilized as a target in bispecific antibodies or T cell receptor constructs to recruit cytotoxic T cells (CTLs). Their highly toxic payload of cell death-inducing enzymes (called granzymes) and a pore-forming protein (perforin) make them one of the most potent killer cells of the human immune system. Bispecific antibodies circumvent evasion strategies of tumor cells by providing a momentary physical link between a T cell and a tumor cell. With one specific binding site the antibody attaches to the CD3 antigen, which is present on all T cells, and with the other one it binds to a surface antigen on tumor cells. The first bispecific cancer antibody recently has been approved for treatment of malignant ascites. At least further ten are in preclinical and clinical development.

Unlike conventional monoclonal antibodies, engineered monoclonal T-cell Receptors (mTCRs) are not restricted to targeting cells via their membrane proteins. Instead, mTCRs use the power of the body's own immune surveillance system, the T-Cell Receptor, as a means of targeting cells differentially expressing any protein, including intracellular ones. This opens up the ability of targeting molecular targets unsuitable for monoclonal antibodies. However, unlike traditional antibodies, soluble mTCRs do not possess an in-built killing function; mTCRs are expressed as fusion proteins to known potent biological effector functions, such as anti-CD3 binding domains for cancer. In this regard, they can be thought of as similar to antibody drug conjugates. A number of mTCR with CD3 payload are emerging for preclinical and clinical development in cancer and infectious diseases.

The report includes a compilation of current active projects in research and development of CD3 targeting antibodies and other biologic constructs. In addition, the report lists company-specific R&D pipelines of CD3 Antagonists. Competitor projects are listed in a tabular format providing information on:

• Drug Codes,
• Target / Mechanism of Action,
• Class of Compound,
• Company,
• Product Category,
• Indication,
• R&D Stage and
• additional comments with a hyperlink leading to the source of information.