Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy‐induced cytokine release syndrome

Matas-Céspedes, Alba; Brown, Lee R.; Mahbubani, Krishnaa; Bareham, Bethany; Higgins, Jackie; Curran, Michelle; Haan, Lolke de; Lapointe, Jean−Martin; Stebbings, Richard; Saeb‐Parsy, Kourosh

doi:10.1002/cti2.1202

Cited by 17 publications

(18 citation statements)

References 59 publications

(180 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following myeloablation by low dose total body irradiation or busulfan treatment, 4 to 7 weeks-old mice are intravenously injected with 60 – 100 x 10 3 human CB-derived CD34 + HSCs, which will home to the bone marrow ( 12 , 17 ). Alternatively, intrahepatic injection of HSCs can be performed in newborn mice ( 27 ).…”

Section: Humanization Methodsmentioning

confidence: 99%

“…Human CD45 + cells may be detected in the mouse peripheral blood on week 4, and they reach a plateau on weeks 8 to 10. The main reconstituted human population is the hCD19 + B cells while hCD3 + T cell count remains rather low until weeks 10 - 12 to reach their maximum level at weeks 18 to 20. hCD14 + monocytes can be found at a density of 1 – 5% of hCD45 + cells ( 12 , 28 ). When human pro-T cells migrate to the mouse thymus, positive and negative selection allows for the establishment of a mature T cell population unable to attack murine tissue ( 29 ) ( Figure 1B ).…”

Section: Humanization Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research

et al. 2021

View full text Add to dashboard Cite

Immunotherapy with checkpoint inhibitors opened new horizons in cancer treatment. Clinical trials for novel immunotherapies or unexplored combination regimens either need years of development or are simply impossible to perform like is the case in cancer patients with limited life expectancy. Thus, the need for preclinical models that rapidly and safely allow for a better understanding of underlying mechanisms, drug kinetics and toxicity leading to the selection of the best regimen to be translated into the clinic, is of high importance. Humanized mice that can bear both human immune system and human tumors, are increasingly used in recent preclinical immunotherapy studies and represent a remarkably unprecedented tool in this field. In this review, we describe, summarize, and discuss the recent advances of humanized mouse models used for cancer immunotherapy research and the challenges faced during their establishment. We also highlight the lack of preclinical studies using this model for radiotherapy-based research and argue that it can be a great asset to understand and answer many open questions around radiation therapy such as its presumed associated “abscopal effect”.

show abstract

Section: Humanization Methodsmentioning

confidence: 99%

Section: Humanization Methodsmentioning

confidence: 99%

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Novel strains of immunocompromised mice have been developed to delay GvHD through elimination of major histocompatibility complex (MHC) class I and/or II expression [92][93][94]. Most recently, the use of NSG-(K b D b ) null (IA) null (NSG-dKO) mice, deficient in murine MHC I and II, was shown to significantly delay GvHD post PBMC engraftment (up to 125 days) [93] and SPMC engraftment (up to 140 days) [77]. This improved survival is consistent with xenoreactivity being predominantly driven by murine MHC class I and II molecules.…”

Section: Modeling Longitudinal Immunotherapy Responsesmentioning

confidence: 99%

“…They demonstrated that SPMCs can be used for the successful engraftment of immune cells, showing hCD45 + ve cells in the circulating blood, spleen and liver of the mice. Similar to the hu-PBL model, engrafted immune cells from SPMC reconstitution was mostly T-cells with an effector memory phenotype [ 77 ].…”

Section: Autologous Io Models: Limitations and Innovationsmentioning

confidence: 99%

Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies

Bareham

Georgakopoulos

Matas-Céspedes

et al. 2021

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

Despite the significant contributions of immunocompetent mouse models to the development and assessment of cancer immunotherapies, they inadequately represent the genetic and biological complexity of corresponding human cancers. Immunocompromised mice reconstituted with a human immune system (HIS) and engrafted with patient-derived tumor xenografts are a promising novel preclinical model for the study of human tumor-immune interactions. Whilst overcoming limitations of immunocompetent models, HIS-tumor models often rely on reconstitution with allogeneic immune cells, making it difficult to distinguish between anti-tumor and alloantigen responses. Models that comprise of autologous human tumor and human immune cells provide a platform that is more representative of the patient immune-tumor interaction. However, limited access to autologous tissues, short experimental windows, and poor retention of tumor microenvironment and tumor infiltrating lymphocyte components are major challenges affecting the establishment and application of autologous models. This review outlines existing preclinical murine models for the study of immuno-oncology, and highlights innovations that can be applied to improve the feasibility and efficacy of autologous models.

show abstract

“…They reported that NSG mice reconstituted with PBMC‐and SPMC better predicted OKT3‐mediated CRS. The SPMC model allows generation of large experimental groups while NSG‐dKO mice are able to mitigate the limitation of early GVHD 85 …”

Section: Pre‐clinical Experiences Of Humanized Micementioning

confidence: 99%

Development of humanized mouse with patient‐derived xenografts for cancer immunotherapy studies: A comprehensive review

Jin

Lan

et al. 2021

Cancer Science

View full text Add to dashboard Cite

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre‐clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient‐derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre‐clinical evaluation of onco‐immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.

show abstract

Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy‐induced cytokine release syndrome

Cited by 17 publications

References 59 publications

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research

Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies

Development of humanized mouse with patient‐derived xenografts for cancer immunotherapy studies: A comprehensive review

Contact Info

Product

Resources

About