CTLA-4

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Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a member of the CD28 superfamily and is a negative regulator of T cell-mediated immune responses. CTLA-4 exhibits cell surface and intracellular constitutive expression on memory T-cells and at a low level by T-regulatory cells (Tregs; 2-4% of circulating CD4+ T cells) (1,2). CTLA-4 primarily inactivates T-cell activity by competing with the CD28 costimulatory molecule (3). CD28 and CTLA-4 share the identical ligands of CD80 and CD86 on antigen-presenting cells; and thus CTLA-4 competes with CD28 function in T-cell survival, proliferation, and recruitment (3,4). In particular, CTLA-4 down-modulates CD4+ helper T-cell activity and enhances Treg immunosuppressive functions (5,6).

CTLA-4 has been shown to play a role in human diseases (1). CTLA-4 acts as a physiological brake on the activated immune system in order to maintain immune homeostasis. Several suppressive mechanisms for T-cell functions have been attributed to CTLA-4. FDA approved Ipilimumab (IgG1 isotype), a monoclonal antibody to CTLA-4, was the first immunotherapeutic drug directed toward CTLA-4 inhibition to demonstrate overall survival benefit in metastatic melanoma (1,7). Another CTLA-4 inhibitor, tremelimumab (IgG2 isotype), has also proven successful in metastatic melanoma and other malignancies (1,7).

Format

Concentrate, Predilute

Volume

0.1 ml, 0.5 ml, 6.0 ml

Intended Use

IVD

Isotype

IgG1

Clone

UMAB249

Antigen

Full length human recombinant protein of human CTLA-4

By Letter

C

Localization

Cell membrane/cytoplasm

Species Reactivity

Human

Positive Control

Tonsil

Source

Mouse Monoclonal

1. Buchbinder EI, McDermott DF. Cytotoxic T-lymphocyte antigen-4 blockade in melanoma. Clinical Therapeutics. 2015; 37:755-63.
2. Baecher-Allan C, et al. Human CD4+CD25+ regulatory T cells. Semin Immunol. 2004 Apr; 16(2):89-98.
3. Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992; 71:1065-8.
4. Azuma M, et al. B70 antigen is a second ligand for CTLA-4 and CD28. Nature 1993; 366:76-9.
5. Hathcock KS, et al. Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. Science. 1993; 262:905-7.
6. Wing K, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008; 322:271-5.
7. Shin DS, Ribas A. The evolution of checkpoint blockade as a cancer therapy: what’s here, what’s next? Curr Opin Immunol. 2015; 33:23- 35.
8. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
9. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.