%0 Journal Article
%T Technical considerations and strategies for generating and optimizing humanized mouse tumor models in immuno-oncology research.
%A Li W
%A Xia C
%A Wang K
%A Xue L
%A Wang Y
%A Yang JY
%A Zhang M
%A Yin M
%A Ju C
%A Miao Z
%A Li Y
%A Zhao X
%A Yang Z
%A Tang R
%A Yang W
%J Int Immunopharmacol
%V 139
%N 0
%D 2024 Sep 30
%M 39033663
%F 5.714
%R 10.1016/j.intimp.2024.112722
%X The field of cancer immunotherapy has experienced significant progress, resulting in the emergence of numerous biological drug candidates requiring in vivo efficacy testing and a better understanding of their mechanism of action (MOA). Humanized immune system (HIS) models are valuable tools in this regard. However, there is a lack of systematic guidance on HIS modeling. To address this issue, the present study aimed to establish and optimize a variety of HIS models for immune-oncology (IO) study, including genetically engineered mouse models and HIS models with human immune components reconstituted in severely immunocompromised mice. The efficacy and utility of these models were tested with several marketed or investigational IO drugs according to their MOA, followed by immunophenotypic analysis and efficacy evaluation. The results of the present study demonstrated that the HIS models responded to various IO drugs as expected and that each model had unique niches, utilities and limitations. Researchers should carefully choose the appropriate models based on the MOA and the targeted immune cell populations of the investigational drug. The present study provides valuable methodologies and actionable technical guidance on designing, generating or utilizing appropriate HIS models to address specific questions in translational IO.