Monoclonal antibodies (mAbs) interact directly with the immune system. These immune-mediated adverse medication responses, such as infusion reactions, cytokine storms, immunosuppression, and autoimmune, represent a danger intrinsic to these immunomodulatory mAbs. To support dosage in humans, a thorough understanding of the possible immunotoxicity of mAbs is required.
Our company has a one-stop antibody service platform that provides a comprehensive suite of in vitro evaluation services that are critical in determining the immunopharmacology, immunotoxicity and immunogenicity of mAbs.
Backgrounds
An antigen-binding fragment (Fab) plus a crystallizable fragment (Fc) make up a full mAb. Fab can bind to tumor-associated antigens, while Fc plays an important role in metabolic pathways as well as in IgG cell function.
Fig.1 Mechanisms of ADCP, ADCC and CDC. (Brennan F. B, et al. 2017)
Effector function will be influenced by the antibody's molecular make-up and isoform. One of these effector activities is antibody-dependent cytotoxicity, which starts when Fc binds to the NK cell's FcγRIII receptor (CD16A). In order to create a membrane assault complex that results in complement-dependent cytotoxicity, Fc can also attach to serum complement molecules (C1q). When Fc interacts with specific macrophage receptors, especially FcRIII, FcRII (CD32A), and FcRI (CD64), antibody-dependent cytophagy is initiated.
Service Overview
Our company offers a range of in vitro assays of varying complexity to characterize.
1) Antibody binding domains of mAb, such as targeted binding and downstream pharmacological effects (e.g. immunosuppression, immune activation, cytokine release) as well as non-targeted binding in humans and animal species used for toxicology studies.
2) Fc-dependent effects such as Fc-mediated cellular activation (e.g. leukocytes, platelets) and cytokine release, complement activation.
3) Product-related factors (sequence, physicochemical properties and impurities) that may affect the pharmacological activity and immunogenicity potential of mAbs.
Our in vitro assay service is critical to the selection of mAb with the best balance of safety and efficacy, to determine if a mAb is a high-risk molecule, and to inform, together with animal data, safe starting doses and escalation regimens in humans.
The specifics of our antibody in vitro evaluation services include, but are not limited to, the following.
- Antibody-dependent cell cytotoxicity (ADCC)
- Complement-dependent cytotoxicity (CDC)
- Antibody-dependent cell phagocytosis (ADCP)
- Binding/blocking experiments
- Antibody endocytosis
- T cell activation
- T cell cytotoxicity
For more information about our services, please feel free to contact us.
Reference
- Brennan F. B, et al. (2017). "In Vitro Assays Supporting The Safety Assessment of Immunomodulatory Monoclonal Antibodies." Toxicology in Vitro. 45(3): 296-308.
Related Services
It should be noted that our service is only used for research, not for clinical use.
