Anti-Mouse CTLA-4 [Clone 9D9] – LALA-PG

Mouse CTLA-4

This recombinant monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

This antibody may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

Activity is directed against mouse Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4)^1,2. Clone 9D9 specifically binds to the extracellular domain of mouse CTLA-4 and is frequently used as a surrogate antibody in murine cancer models to mimic the effects of human anti-CTLA-4 therapies^1,3.

CTLA-4 is a transmembrane inhibitory receptor and a member of the CD28 immunoglobulin superfamily². It serves as a critical immune checkpoint by competing with the costimulatory receptor CD28 for binding to B7-1 (CD80) and B7-2 (CD86) ligands on antigen-presenting cells^2,3.

Because CTLA-4 has a significantly higher affinity for B7 ligands than CD28, it effectively out-competes stimulatory signals, leading to the downregulation of T-cell activation and the maintenance of peripheral tolerance^2,4. Clone 9D9 was identified as a potent inhibitor of these interactions, allowing for enhanced T-cell responses in the context of tumor immunity^1,3.

Mechanism of Action: Clone 9D9 acts as a dual-function antibody to promote anti-tumor activity^1,5:

1. Checkpoint Blockade: It sterically blocks the interaction between CTLA-4 and its B7 ligands, preventing the inhibitory signal and allowing CD28-mediated costimulation to proceed^1,4.

2. Treg Depletion: Due to its mouse IgG2b isotype, 9D9 can facilitate the depletion of intratumoral Regulatory T cells via Fc-𝛾 receptor-mediated mechanisms, such as antibody-dependent cellular phagocytosis (ADCP), thereby reducing immunosuppression within the tumor microenvironment^5,6.

CTLA-4 is primarily expressed on the surface of activated T lymphocytes². It is constitutively expressed at high levels on Regulatory T cells (Tregs), where it is essential for their suppressive function^3,4. In resting naive T cells, CTLA-4 is largely sequestered in intracellular vesicles and is rapidly translocated to the cell surface following T-cell receptor (TCR) stimulation^2,4.

Binds to B7-1 (CD80) and B7-2 (CD86) with higher affinity than CD28.

1. Selby MJ, Engelhardt JJ, Quigley M, et al. Anti-CTLA-4 antibodies of IgG2a isotype exhibit enhanced antitumor activity through Fc-mediated depletion of intratumoral regulatory T cells. Cancer Immunol Res. 1(1):32-42. 2013.
2. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 3(7):611-618. 2002.
3. Peggs KS, Quezada SA, Chambers CA, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 206(8):1717-1725. 2009.
4. Walker LS, Sansom DM. The emerging role of CTLA-4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 11(12):852-863. 2011.
5. Bulliard Y, Jolicoeur R, Zhang J, et al. OX40 engagement depletes intratumoral Tregs via activating Fc-𝛾Rs, leading to antitumor efficacy. Immunol Cell Biol. 92(6):475-480. 2014.
6. Quezada SA, Peggs KS, Curran MA, Allison JP. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Exp Med. 203(9):2119-2135. 2006.