期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.619236
关键词
immunodeficient mice models; immunotherapy; human hematopoiesis; xenotransplantation models; immune reconstitution
类别
资金
- Francis Crick Institute
- Cancer Research UK [FC0010045]
- UK Medical Research Council [FC0010045]
- Wellcome Trust [FC001045]
- UK Biotechnology and Biological Sciences Research Council [BB/S017097/1]
- Blood Cancer UK
- BBSRC [BB/S017097/1] Funding Source: UKRI
Immunotherapy shows promise in cancer treatment, yet challenges remain, including the lack of suitable mouse models. Improved immunodeficient mice offer opportunities for comprehensive evaluation of therapeutic strategies and advancement in human hematopoietic research.
Immunotherapy has established itself as a promising tool for cancer treatment. There are many challenges that remain including lack of targets and some patients across various cancers who have not shown robust clinical response. One of the major problems that have hindered the progress in the field is the dearth of appropriate mouse models that can reliably recapitulate the complexity of human immune-microenvironment as well as the malignancy itself. Immunodeficient mice reconstituted with human immune cells offer a unique opportunity to comprehensively evaluate immunotherapeutic strategies. These immunosuppressed and genetically modified mice, with some overexpressing human growth factors, have improved human hematopoietic engraftment as well as created more functional immune cell development in primary and secondary lymphoid tissues in these mice. In addition, several new approaches to modify or to add human niche elements to further humanize these immunodeficient mice have allowed a more precise characterization of human hematopoiesis. These important refinements have opened the possibility to evaluate not only human immune responses to different tumor cells but also to investigate how malignant cells interact with their niche and most importantly to test immunotherapies in a more preclinically relevant setting, which can ultimately lead to better success of these drugs in clinical trials.
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