Anti-Mouse CTLA-4 Monoclonal Antibodies

PA007380.m2b: In vivo Grade Recombinant Anti-mouse CTLA-4 Monoclonal Antibody, Mouse IgG2b Kappa (Clone: 9D9)

Recombinant Mouse IgG2b Monoclonal Antibody. 
Clone: 9D9.
Isotype: Mouse IgG2b kappa.
Source: The anti-mouse CTLA-4 monoclonal antibody (clone: 9D9) was produced in mammalian cells.
Specificity/Sensitivity: The in vivo grade recombinant mouse monoclonal antibody (clone: 9D9) specifically binds to the mouse CTLA-4 protein.
Applications: ELISA, flow cytometry, neutralization, functional assays such as bioanalytical PK and ADA assays, and those assays for studying biological pathways affected by the mouse CTLA-4 protein. 
Form of Antibody: 0.2 uM filtered solution, pH 7.4, no stabilizers or preservatives.
Endotoxin: < 1 EU per 1 mg of the protein by the LAL method.
Purity: >95% by SDS-PAGE under reducing conditions.

Shipping: The antibody is shipped with ice pack. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
12 months from date of receipt, -20 to -70°C as supplied.
1 month from date of receipt, 2 to 8°C as supplied.

Background

The 9D9 antibody blocks the mouse cytotoxic T lymphocyte antigen-4 (CTLA-4). Blocking CTLA-4 removes an inhibitory signal from reducing the activity of T lymphocytes.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that competes with the stimulatory CD28 for binding to B7 on antigen presenting cells. CTLA-4 and CD28 are both presented on the surface of T-cells.

Related Recombinant IgG Reference Antibodies:
Recombinant mouse lgG2b isotype control antibody
Recombinant mouse IgG2c LALAPG isotype control antibody
Recombinant mouse IgG2a LALAPG isotype control antibody

Syd Labs provides the following research grade anti-CTLA-4 antibody biosimilars:
Ipilimumab Biosimilar, research grade, anti-human CTLA-4 monoclonal antibody
Tremelimumab Biosimilar, research grade, anti-human CTLA-4 monoclonal antibody

Recombinant CTLA-4 Proteins:
Biotinylated Human CTLA-4 Protein
Cynomolgus CTLA-4 Protein
Human CTLA-4 Protein

References of Anti-mouse CTLA-4 Monoclonal Antibody:

Induced PD-L1 expression mediates acquired resistance to agonistic anti-CD40 treatment.
Zippelius, A., et al. Cancer Immunol Res. 2015 Mar;3(3):236-44. doi: 10.1158/2326-6066.CIR-14-0226. PMID: 25623164
Concomitant CTLA-4 blockade further improved the therapeutic efficacy of this combination. ...Owing to their distinct immunologic mechanisms of action, concomitant blockade of PD-1 and CTLA-4 has shown superior therapeutic activity in patients with melanoma as compared with either of the antibodies alone. ...Intriguingly, we have noticed an increase in the frequency of CTLA-4–expressing CD8+ T cells (Supplementary Fig. S1F and S1G) upon agonistic anti-CD40 treatment. ...When combining both anti–PD-L1 and anti–CTLA-4 with anti-CD40 treatment, more than 90% of tumors were rejected. ...By integrating CTLA-4–blocking antibodies into the anti-CD40/PD-L1 and anti-CD40/PD-1 treatment regimen, we were able to further enhance durable tumor rejection. ...Although a clinical trial evaluating the agonistic anti-CD40 antibody RO7009789 in combination with the CTLA-4–blocking antibody tremelimumab is currently under way at the University of Pennsylvania, to our knowledge, a combination with PD-1/PD-L1–blocking antibodies has not yet been attempted in patients with cancer.
Tags: anti-mouse CTLA-4 9D9; anti-mouse CTLA-4 9D9 mAb

Combined targeting of costimulatory (OX40) and coinhibitory (CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity.
Redmond, W. L., et al. Cancer Immunol Res. 2014 Feb;2(2):142-53. doi: 10.1158/2326-6066.CIR-13-0031-T. PMID: 24778278
CTLA-4 is a negative regulatory protein that serves as a checkpoint inhibitor to limit T-cell responses by attenuating T-cell proliferation and cytokine production. ...OX40 and CTLA-4 are both upregulated on CD4 and CD8 T cells shortly after TCR stimulation and are constitutively expressed on Tregs. ...Preclinical data have shown that monotherapy with anti-OX40 or anti-CTLA-4 has limited therapeutic efficacy against many tumor types, suggesting that combination immunotherapy likely will be required to generate optimal therapeutic responses. ...These data provide insight into the mechanisms by which the combined anti-OX40/anti-CTLA-4 immunotherapy drives potent polyclonal effector T-cell (Teff) responses and suggest that the clinical combination of these agents may offer a novel means of boosting tumor immunotherapy in patients with cancer. ...Monotherapy with anti-OX40 or anti-CTLA-4 had limited effects on tumor growth or survival, but the combined immunotherapy significantly enhanced tumor regression and survival.
Tags: anti-mouse CTLA-4 9D9 in vivo; anti-mouse CTLA-4 9D9 in animal model

Combinatorial PD-1 blockade and CD137 activation has therapeutic efficacy in murine cancer models and synergizes with cisplatin.
Wei, H., et al. PLoS One. 2013 Dec 19;8(12):e84927. doi: 10.1371/journal.pone.0084927. PMID: 24367702
Programmed Death 1 (PD-1) protein is a co-inhibitory receptor on T cells with a structure similar to that of CTLA-4 but with a distinct biologic function and ligand specificity. ...Based on published evidence indicating a therapeutic potentials in several tumor models we tested mAbs to CD137, CD40, CTLA-4, PD-1, TIM-3 and LAG-3 [34,35], as single agents and in combinations. ...The following monoclonal antibodies (mAb) used in animal experiments were purchased from BioXcell (West Lebanon, NH): anti-CD137 (Clone lob12.3), anti-PD-1 (Clone RMP1-14), anti-CTLA4 (Clone 9D9), anti-NK1.1 (Clone PK136), anti-CD8 (Clone 2.43), anti-CD4 (Clone GK1.5) and control (Clone 2A3). ...Mice were injected intraperitoneally (i.p.) with 3 × 106 ID8 cells in 0.1 mL of PBS. On days 10 and 14 after tumor inoculation, mice were injected i.p. with 0.5 mg of each mAb in total 0.5 mL of PBS as shown in the figure legends. ...Mice which had been transplanted i.p. with ID8 cells were euthanized 7 and 14 days after they had been injected with the anti-PD1, anti-CD137, anti-PD1/CD137 or control as in the therapy experiments.
Tags: anti-mouse CTLA-4 9D9 mAb in animal model; function of anti-mouse CTLA-4 9D9

Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.
Bulliard, Y., et al. J Exp Med. 2013 Aug 26;210(9):1685-93. doi: 10.1084/jem.20130573. PMID: 23897982
To evaluate this, we chose an antagonist antibody (clone 9D9, murine IgG2b) targeting the T cell antigen CTLA-4, which functions to negatively regulate T cell proliferation upon signaling. ...Similar to the expression profile of GITR, CTLA-4 was expressed by intratumoral CD4+ T cells, most notable the T reg cell population. ...In general, the depletion of T cell populations correlated with the overall level of target antigen expression, although with anti–CTLA-4 treatment this observation was less clear with an overall reduction of intratumoral CD4+ T cells on day 5. ...Interestingly, ipilimumab, an antagonist antibody targeting CTLA-4 with human IgG1 framework, has shown efficacy in metastatic melanoma patients. ...In contrast, another antagonist antibody targeting CTLA-4, tremelimumab, is a human IgG2 antibody and has a lower A/I ratio.
Tags: anti-mouse CTLA-4 9D9; anti-CTLA-4 clone 9D9

Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production.
Curran, M. A., et al. PLoS One. 2011 Apr 29;6(4):e19499. doi: 10.1371/journal.pone.0019499. PMID: 21559358
We find that combining αCTLA-4 and α4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. ...The addition of CTLA-4 blockade further increased IFN-γ production from CD4+ effector T-cells in the vaccine draining node and the tumor. ...Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). ...This study shows that combining T-cell co-inhibitory blockade with αCTLA-4 and active co-stimulation with α4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. ...The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) is induced on T-cells shortly after activation and functions to attenuate their proliferation, IL-2 production, and contact time with antigen presenting cells (APC).
Tags: bioactivity of anti-mouse CTLA-4 9D9; bioactivity of anti-mouse CTLA-4 9D9 mAb

For more references about Anti-mouse CTLA-4 Monoclonal Antibody please contact our scientific support team with message@sydlabs.com.