Immunotherapy harnesses a patient’s own immune system to combat cancer, with numerous benefits compared to conventional treatments such as chemotherapy and surgical removal.1 Among different immunotherapy treatments, immunomodulatory antibodies that target immune checkpoints such as CTLA4 and PD-1 have demonstrated recent success in the clinic. Ipilimumab (anti-CTLA4) and nivolumab (anti-PD1) are each individually FDA-approved immunotherapy treatments for advanced metastatic melanoma. In fact, the number of immunotherapy drugs in pipelines under development has grown from 2,030 to 3,876, a whopping 91% increase from 2017 to 2019.2
One major challenge is the development of appropriate animal models for immunotherapy.3 Due to the complexity of the immune system and tumor, it is difficult to model multiple different cell types that function in a tumor microenvironment based on a single cell type. Offering replicability and specificity of purpose, mouse models provide a reliable option for translational research. Better animal models in immunotherapy are in rising demand from the biopharmaceutical community.
As a leading model provider focused on the field of immunotherapy and antibody discovery, Biocytogen offers a line of target-humanized mice models that covers a growing portfolio of immune checkpoints and cytokines. Biocytogen’s humanized mice models are strategically designed to maintain the target’s biological functions, preserve a normal immune system, and optimize physiological humanized protein expression. This maximizes the chance of translational success of in vivo efficacy evaluation of immune checkpoint antibodies or inhibitors in clinical trials. Some highlights of these models include hCD3e (for bispecifics), hPD-1, hCD40, hCD47, hOX40, hCTLA-4, and IL4/ILRA (as inflammation/allergy models).
Furthermore, Biocytogen offers a wealth of double and triple target-humanized mouse models, such as the hPD-1/CTLA4, hPD1/hOX40, and B-hPD-L1/hSIRPA/hCD47 mice, for the development of combo therapy, an increasingly important treatment due to its improved response rate, lower toxicity, and potentially lower drug resistance.4
In addition to target-humanized models, Biocytogen has also developed the immunodeficient B-NDG mice and a class of humanized mice based on B-NDG background for tumor model generation using patient-derived xenografts (PDXs). The B-NDG mouse is the most immunodeficient mouse model with complete lack of mature T, B, and natural killer (NK) cells and is a great host for CAR-T efficacy evaluation. Although B-NDG has been widely used in human-derived cell engraftment, the maintenance and differentiation functions of hematopoietic cells and the development of immune cells inside the mouse is limited. To address this problem, Biocytogen developed B-NDG/hIL-15 via humanization of the cytokine IL15 gene based on a B-NDG background. This model has been shown to support a higher proportion of human NK cells that express functional proteins compared to the original B-NDG mouse, thus offering an ideal model for in vivo efficacy examination of NK cell therapy.
Severe xenogeneic graft-versus-host disease (xeno-GVHD) in immunodeficient mice could limit the therapeutic window of experimentation and precise immune response analysis in human peripheral blood mononuclear cell (PBMC) engraftment in B-NDG mice. For this issue, Bicoytogen has developed B-NDG B2m KOplus mice, which expresses the B2m gene fused in the FcRn gene while the murine B2m gene is knocked out. This mouse shows no difference in the metabolism of IgG drugs compared with that of wild-type mice. The B-NDG B2m KOplus mice is thus suited for the investigation of in vivo mechanisms behind xeno-GVHD and antibody efficacy.
Biocytogen is committed to providing powerful tools that revolutionize how antibody therapeutics are developed. Launched last year, RenMab is a fully human antibody mouse that has the entire variable domain of the heavy chain and kappa light chain genes replaced with human antibody genes via a one-step in situ chromosome engineering technology. This year, Biocytogen will continue to expand its unique class of RenMab mice model offerings to include RenLite (common light chain) and RenNano (heavy chain only) for bispecific and single-domain antibodies, respectively. With a diverse catalog of antibody- and target-humanized models, Biocytogen has envisioned a platform that can significantly maximize the success of antibody therapeutics in clinical trials.
Visit www.biocytogen.com to learn more about Biocytogen’s capability and latest echntology in antibody development and immunotherapy research