The immunotherapy of tumors mainly relies on the monitoring and elimination of cancerous cells by the in vivo immune system mainly composed of immune cells such as T cells. However, most tumors have methods to circumvent the immune system. In order to activate and exert the anti-tumor effect of the immune system as much as possible, Creative Biolabs provides biopharmaceutical workers all over the world with a variety of in vivo testing services in transgenic mice to help our customers evaluate the immunogenicity of predicted T-cell epitopes.
Screening and Detection of Immunogenic Peptides
After screening the target antigen by various methods and predicting its potential T cell epitope, the next step in drug development is to evaluate its drug-making ability. In cancer immunotherapy, the affinity with T cell epitopes is the main reference for peptide efficacy, and we need to test its immunogenicity in the in vivo or in vitro models. By processing and presenting the screened epitopes in the major histocompatibility complex (MHC), these peptides may undergo different processes depending on their source, and finally we can test their binding ability to HLA alleles by immune-modifying T cells or mouse models. This method does not need to purify the whole protein and can minimize the investment of money and time in the research.
HLA-DR4 and HLA-DR1 Transgenic Mouse Models
HLA-DR1+/+/IA+/+ and HLA-DR4+/+/IE0/0 transgenic mice provide a good model for us to observe the immune response of human CD4+ T cells and can be used to identify MHC class II peptides. Analogous to MHC class I, MHC class II peptides derived from tumor-associated proteins, such as p53, can be synthesized and used to immunize DR4 and DR1 transgenic mice, studies have shown that this method can identify new p53 peptides. In this method, immunize mice with incomplete Freund’s adjuvant twice, and stimulate spleen cells in vitro with the same peptide after immunization, then CD4+ T cells were tested for peptide-pulsed dendritic cells, tumor lysis dendritic cells or direct specific response to tumor cells. And the results showed that spleen cell-specific DR of p53 peptide immunized animals inhibited proliferation and production of cytokines.
Because the T cell banks of these humanized HLA transgenic mice were molded by human class II molecules, they showed the same HLA limitations as humans, suggested potential triggering mechanisms and autoantigens, and identified similar epitopes observed in humans. Creative Biolabs’ MHC II transgenic mice models overcome the complexity of MHC and strong linkage disequilibrium between different class II gene and other issues, not only can be used in the field of cancer immunotherapy but also can help researchers to establish model of other autoimmune diseases.
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