Home Educational Resources Choosing Anti-CTLA-4 Antibodies

How to Choose an Anti-CTLA-4 Antibody for Your Research

CTLA-4 Introduction

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory receptor predominantly expressed on T cells. CTLA-4 maintains immune homeostasis during T-cell activation. CTLA-4 signaling results in immunosuppression and restricted T cell function, and its deficiency results in autoimmunity. Through a process called co-stimulation, the activation of T cells is dependent on the binding of CD28 to its ligands, CD80 (B7-1) and CD86 (B7-2). CTLA-4 preferentially binds to CD80/CD86 and transmits inhibitory signals to prevent CD28-mediated T-cell activation. CTLA-4 is constitutively expressed by regulatory T cells (Tregs), which prevents T cells from killing other cells, including cancer cells. Anti-CTLA-4 antibodies block CTLA-4 binding with CD80 and CD86, and the blockade of CTLA-4 enhances anti-tumor immune responses. The major biological effects and the underlying mechanism of action of CTLA-4-blocking antibodies are illustrated in the figure below:

CTLA-4-blocking antibodies

Image Description: Biological effects of CTLA-4-blocking antibodies.

CTLA-4-blocking antibodies (represented as α-CTLA-4 in the diagram) can promote antibody-dependent cellular cytotoxicity (ADCC), especially when bound to an Fc receptor on an antigen-presenting cell (APC). Because CD4+CD25+ Tregs express higher amounts of CTLA-4 than conventional T cells, they are more prone to anti-CTLA-4 antibody-induced ADCC than conventional T cells. Additionally, anti-CTLA-4 antibodies can bind to CTLA-4 on the surface of the Tregs and prevent it from counter-regulating the CD28-mediated co-stimulatory pathways. Concurrently, anti-CTLA-4 antibodies can also promote T cell responses by blocking CTLA-4 on the surface of conventional T cells as they undergo activation. (Source: Waldman et. al., 2020)

Anti-CTLA-4 Antibody Reactivity

The first step in deciding which anti-CTLA-4 antibody is appropriate for your research project is to identify the species reactivity required for your experimental model. Bio X Cell offers anti-mouse, anti-human, and anti-rat CTLA-4 antibodies. Which antibody product to choose would depend on the species of your experimental model. For example, if you are working with mice expressing murine CTLA-4 protein, you want to choose an anti-mouse CTLA-4 antibody. If you are using human cells in culture or humanized mice expressing human CTLA-4, then you want to choose an anti-human CTLA-4 antibody.

Anti-Mouse CTLA-4 Antibody Clones

Table 1: Detailed Comparison of anti-mouse CTLA-4 Antibody Clones

Recombinant anti-mouse CTLA-4 Antibody Clones

Bio X Cell also offers recombinant chimeric versions of our three anti-mouse CTLA-4 antibody clones. RecombiMAb™ antibodies are provided as chimeric antibodies with mouse constant regions instead of the typical rat or hamster constant regions. This ensures reduced immunogenicity in sensitive mouse models. Select RecombiMAb™ antibodies are also available in multiple Fc-silenced versions. These Fc-silenced versions have mutations in the Fc fragment of the antibody, rendering them unable to bind to endogenous Fcγ receptors.

Table 2: Detailed Comparison of Recombinant anti-mouse CTLA-4 Antibody Clones

Anti-Human CTLA-4 Antibody Clones

Bio X Cell also offers multiple anti-human CTLA-4 antibodies for use in humanized mouse models or immunoassays. These include clones BN13 and an Ipilimumab biosimilar antibody.

Table 3: Detailed Comparison of anti-human CTLA-4 Antibody Clones

Anti-Rat CTLA-4 Antibody Clone

Bio X Cell also offers an anti-rat CTLA-4 antibody, clone WKH203 (Lin and Hunig 2003), for use in experiments involving rat models. The WKH203 monoclonal antibody was generated against a purified rat CTLA-4hIg fusion protein, and this antibody neutralizes CTLA-4 in vitro.

Recombinant CTLA-4-Ig Fusion Protein

Table 4: Details of InVivoMAb™ and InVivoPlus™ versions of Recombinant CTLA-4-Ig (hum/hum)