Cytotoxic lymphocyte associated molecule 4 CTLA 4 CD152 - Biotech, Pharma and Life Science Channel
Cytotoxic lymphocyte-associated molecule-4 (CTLA-4, CD152) is a member of the CD28 receptor family which is expressed on the surface of Helper T cells. CTLA-4 is similar to the T-cell costimulatory protein CD28, and both molecules bind to their ligands of the B7 family: B7-1 (CD80) and B7-1 (CD86) on antigen-presenting cells. CTLA-4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal.
The clinical disaster with the supra-agonistic anti-CD28 antibody TGN-1412 dampened for some time enthusiasm in the B7-CD28/CTLA-4 co-stimulatory pathway. The increasing commercial success of the CTLA-4-Ig fusion protein abatacept (2009 sales of US$ 602 mln) in rheumatoid arthritis and the anti-cancer activity of anti-CTLA-4 antibodies have contributed to renewed interest in this pathway. Fusion proteins containing CTLA-4 act by inhibiting B7-mediated co-stimulation of T cells via the CD28 receptor and find utility to treat T-cell mediated autoimmune diseases or to induce immune tolerance. Newer developments aim at increasing effector functions.
In contrast, molecules inhibiting CTLA-4 work by reducing the B7-CTLA-4-mediated downregulation of T-cell activation leading to increased T cell activity. Use of CTLA-4 blockers in cancer relieves the inhibition of T-cells allowing them to identify the over-expressed tumor proteins and in turn naturally attack cancer cells without harming healthy tissues.
News Articles
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Companies
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Medical and Biotech [MESH] Definitions
Lippia
A plant genus of the family VERBENACEAE. Lippsidoquinone; TRITERPENES; SESQUITERPENES; and THYMOL have been found in this genus. Plant extracts have cytotoxic activity. It is sometimes called Mexican oregano but that confuses it with real oregano (ORIGANUM).
T-cell Antigen Receptor Specificity
The property of the T-CELL RECEPTOR which enables it to react with some antigens and not others. The specificity is derived from the structure of the receptor's variable region which has the ability to recognize certain antigens in conjunction with the MAJOR HISTOCOMPATIBILITY COMPLEX molecule.
Calreticulin
A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
Integrin Alpha4beta1
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
Receptors, Fibrinogen
Receptors that bind FIBRINOGEN through distinct adhesive sequences on the fibrinogen molecule. Although MACROPHAGE-1 ANTIGEN is considered an important signaling molecule for fibrinogen interaction, a variety of INTEGRINS from all three major families, (beta1, beta2, and beta3) have been shown to bind fibrinogen.
