In vitro and ex vivo assays are straightforward and able to provide a preview of the immunogenicity of biotherapeutic drug candidates. However, these assays also have some limitations. For instance, the frequency of antigen-specific T cells in naïve cell population derived from peripheral blood mononuclear cells (PBMCs) is quite low. Therefore, some positive response may be neglected. Moreover, various cell types, such as NK cells, NKT cells, CD4+ and CD8+ T cells, can secret many different cytokines, which interferes the measurement of cytokine production of a specific cell type, e.g. CD4+ T cells. On the other hand, NK cells, CD8+ T cells and other cell types play supportive roles in CD4+ T cell activation. Thus, tuning the balance between removal of irrelevant responses and reservation of supportiveness for the ex vivo culture becomes a major obstacle to more accurate assessments.
Diadigom of immuno reactions after therapeutic administration. (Lollini et al. 2006)
Creative Biolabs offers one-stop in vivo immunogenicity assessment service taking advantages of our exclusive Sensitive Immunogenicity Assessment Technology® (SIAT®) platform. SIAT® in vivo immunogenicity assessment employs various animal models including HLA transgenic mice and humanized mice to deliver the most straightforward evaluation of both innate and adaptive human immune responses without putting patients at risk.
The use of normal mouse models to study the immunogenicity of biotherapeutic drugs is flawed. Biotherapeutic drugs that are non-immunogenic in human may be foreign to mice and therefore elicit immune responses in mice. In collaboration with partners, Creative Biolabs has developed several enhanced mouse models to conduct in vivo immunogenicity assessment. The featured mouse models are described below.
HLA transgenic mice
Specific human HLA genes are incorporated into HLA class II-deficient mice to construct a mouse model that expresses human HLA II molecules other than mouse ones. These mice are able to process and present epitopes in complex with human HLA II and subsequently activate the epitope-specific T cells. This kind of mouse model is of great help in evaluating, predicting, and comparing the immunogenicity of structural similar biotherapeutic drugs.
Humanized mouse models
In the HLA transgenic mice, antigens are presented with human HLA molecules to mouse TCR, which confines the usage of HLA transgenic mice for testing the immunogenicity of a human biotherapeutic drug candidate. Therefore, humanized mouse models have been developed to improve this situation. Immunodeficient SCID-SID-NSG mice are engrafted with functional human hematopoietic stem cells (CD34+), liver and/or thymus so that a functional human immune system is reconstructed. This kind of humanized mouse models can be used to study the immunogenicity of biotherapeutic drugs in a full human immune system.
SIAT® in vivo immunogenicity assessment service provides versatile assays for the investigation of immunogenicity of novel candidate drugs, such as local lymph node assay, hypersensitivity response measurement, and cutaneous anaphylaxis assays. Our service will help to accelerate the development of your novel drug candidates by systematically addressing the evaluation of immunogenicity, which promises a clear vision and guideline before entering clinical trials.
More SIAT® Immunogenicity Related Services at Creative Biolabs
In Silico Immunogenicity Assessment
In Vitro Class II HLA Binding Assay
Ex Vivo Immunogenicity Assessment
DC-T Cell Proliferation Assay
Antigen Presentation Assay
In Vivo Immunogenicity Assessment
Anti-drug Antibodies (ADA) Assays