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3 minute read
Mouse models have been the workhorses of preclinical immuno-oncology (IO) research, and advances in mouse model development have expanded to applications for nearly all types of solid tumors and hematological malignancies. Preclinical evaluation of experimental immunotherapies has been advanced by syngeneic and humanized mouse models.
Syngeneic mice are one of the most established types of models used in cancer research, whereas humanized mice are a contemporary mouse model that has been critical to the screening of immunotherapeutic agents. Here we highlight features of syngeneic and humanized mouse models and define which models are most relevant to different phases of preclinical IO research.
Syngeneic Tumor Models
Syngeneic tumor models are created by transplantation of tumor cell lines into immunocompetent mice with the same genetic background as the cell line.[1] Tumors can be transplanted intravenously or subcutaneously into mice and typically grow rapidly over several weeks. Different types of tumor cell lines can be used in this type of model, including spontaneous, transgenic, or carcinogen-induced tumor cell lines. Syngeneic mouse models are best suited for screening novel IO agents or gaining insight into anti-tumor responses in the context of an intact immune system. Given the rapid growth of tumors in syngeneic mice, these models are less well suited to studying early events in tumor growth associated with cancer stem cells or understanding the contributions of heterogeneous tumor microenvironments, and these models typically do not recapitulate the mutational heterogeneity observed in human tumors.[2]
Champions Oncology offers an extensive suite of syngeneic models, meticulously curated to support your groundbreaking investigations within a robust and intact immune environment. We harness advanced biomedical techniques to deliver comprehensive data with accurate and reliable experimental endpoints:
- cutting-edge flow cytometry for detailed characterization of immune cell populations,
- western blot analysis to quantify the expression of pivotal cancer and immune signaling proteins,
- immunohistochemistry for the precise localization of these proteins within the tissue architecture.
Explore our syngeneic tumor model offering here.
Humanized Tumor Models
Humanized tumor models are a more recent addition to preclinical IO research that provide valuable insight into how individual tumors from patients (xenografts) respond to experimental therapies. Prior to the development of humanized mouse models, human xenograft models were used for screening cytotoxic or immunotherapeutic agents like chimeric antigen receptor (CAR) T cells[3], and these models use human tumor cell lines or patient-derived specimens transplanted into immunocompromised host mice. Different immunocompromised models can be used, including athymic mice that lack T cells or severe combined immunodeficiency (SCID) models that lack all adaptive immune responses. Humanized mice have been engineered from immunocompromised mouse strains that include genetic mutations in other adaptive immune functions that allow for the engraftment of human hematopoietic cells. The NOD/SCID IL2rγ chain knockout (NSG) mouse (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) is one of the most used combined immunodeficiency models that can be engrafted with human hematopoietic cells and primary human tumors.[4] These patient-derived xenograft (PDX) models are useful for evaluating experimental IO therapies in the context of the human immune system and can use human immune cells from the same or different donor as the tumor source. PDX models are suited to evaluating experimental therapies in the context of a genetically heterogeneous tumor and better recapitulate aspects of the tumor microenvironment.
(Download our case study "Using Champions' Prostate PDX Models for Preclinical Validation of a Novel, PSMA-directed BiTE" to see how Amgen used our humanized models to test a novel PSMA-targeted BiTE)
Tumors can be grafted either orthotopically or subcutaneously and this also impacts how tumors grow and respond to experimental treatments.[5] Given the heavily modified nature of the NSG immune system, these models do not always reflect responses observed in humans during clinical trials. Nonetheless, NSG mice and similarly modified humanized mice offer valuable insights into the efficacy of IO candidates.
Champions Oncology's state-of-the-art humanized mouse models are tailored to harness the power of the human immune system. Our portfolio offers a suite of options crafted to empower your scientific investigation:
- engraftment of cell therapies,
- adoptive transfer of human PBMCs and NK cells,
- engraftment of CD34+ hematopoietic stem cells from cord blood for full reconstitution of the human immune system.
Learn more about our humanized models offer here.
Mouse models are constantly being refined and improved to better reflect human physiology. Both syngeneic and humanized mouse models serve as valuable tools for preclinical IO research and accelerate the screening and evaluation of novel therapeutics.
