Table 1

Preclinical immuno-oncology models

Model	Applications	Advantages	Limitations
Cell line-derived xenografts (CDX)	Candidate screening (efficacy, pharmacokinetics, pharmacodynamics) Subcutaneous, surgical implant into the tissue/organ of interest (orthotopic implantations) Wide range of oncology indications/therapeutics including cell-based therapies Some models can be used to evaluate metastatic disease	Logistically easy Readily available Industry ‘standard’ Luciferase expressing versions exist	Can be poorly predictive Established decades ago; genetic drift is possible resulting in the same cell line performing differently in different labs Immune-deficient mouse required; hard to evaluate immune-mediated responses
Patient-derived xenografts (PDX)	Drug screening studies Efficacy studies Pharmacodynamic studies Investigation of drug resistance mechanisms	Histological ‘fidelity’ to original patient tumor Extensively characterized Reported to be predictive for clinical outcome25	Immune-deficient mouse required Logistically challenging to establish Some tumor types have limited availability Slower growing (generally) versus human xenografts Increased expense versus human xenografts
Humanized immune system mice	Investigate therapeutics that do not have a murine homolog or surrogate antibody Investigate aspects of human immune response in mouse model	Evaluate human antibodies or antibodies to human gene targets Can use CDX or PDX lines Mimics some aspects of human immune system	Expensive studies Suboptimal immune system Models allograft immunity Graft-versus-host disease
Syngeneic cell lines	Drug screening studies Efficacy studies Mechanism of action	Intact immune system Logistically easy Readily available Luciferase expressing versions exist	Can be poorly predictive24 Established decades ago; genetic drift is possible resulting in the same cell line performing differently in different labs Overall number of models is limited
Genetically engineered mouse models	Studies with specific driver mutations Mechanism of action Targeting tumor microenvironment (TME)	Faithful stromal biology (TME) Relevant genetic drivers Establishment of transplant-derived models	Logistically challenging to establish Expensive licenses Few neo-antigens Rolling study enrollment
Tumor organoids/ spheroids	Assess impact of tumor heterogeneity Develop tumor/immune cell models Assess appropriate therapy choice	Ease of development Ability to create multiple organoids from single patient sample Biomarker assessment	Success rate of going from tumor to organoid culture Lack of key elements from the TME