Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology

Yao, Li‐Chin; Aryee, Ken‐Edwin; Cheng, Mingshan; Kaur, Pali; Keck, James; Brehm, Michael A.

doi:10.1007/978-1-4939-9145-7_15

Cited by 55 publications

(36 citation statements)

References 20 publications

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“…Subsequently, in order to test the effect of curcumin on human breast cancers and to model tumor growth and metastases, we would test the effect of topical curcumin on PDX mice [28]. Using humanized mice, it would be of interest to test curcumin's cytotoxic impact on ER/PR+, Her2+, and Triple Negative breast cancer subtypes to see if there are any differences in effects or outcomes.…”

Section: Approaches and Methodsmentioning

confidence: 99%

Targeted Transdermal Delivery of Curcumin for Breast Cancer Prevention

Atlan

Neman

2019

IJERPH

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N.B. This manuscript is based on the research concept submitted to the “Global Challenge to Prevent Breast Cancer” idea showcase and competition, launched in 2018 by the California Breast Cancer Research Program (CBCRP), which was subsequently selected for publication. The hypothesis, methods, and discussion put forth here are thus proposed concept studies, which could eventually be elucidated in the future. Curcumin is an herbal supplement, shown in preclinical studies to have antioxidant, anti-inflammatory, and antitumoral properties that we believe can be harnessed for breast cancer prevention. However, due to its poor absorption when consumed orally, curcumin’s anticancer effects have not yet been exploited to their full therapeutic potential. Incorporating existing research that focuses on the optimization of curcumin’s bioavailability and the latest transdermal delivery technology, we propose, below, a hypothetical in vivo study to test whether a targeted daily dose of bioavailable curcumin has a cytotoxic effect on cancer cells, potentially reducing the incidence of breast cancer over time. Our ultimate objective is to adopt innovative methods to create curcumin-infused bio-textiles offering transdermal, targeted drug delivery, simply through contact with the skin. We would use this fabric to create disposable bra inserts for an effortless, daily breast cancer prevention regimen for healthy women. It would be essential that the cost of these inserts remain reasonable, but if successful, curcumin is readily available, affordable and non-toxic, and could thus be a preventive measure that would be beneficial for women from all socio-economic backgrounds.

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Section: Approaches and Methodsmentioning

confidence: 99%

Targeted Transdermal Delivery of Curcumin for Breast Cancer Prevention

Atlan

Neman

2019

IJERPH

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“…However, in order to effectively evaluate other types of immunotherapy, in particular ICIs, it is necessary to reconstruct the immune system, ideally from the same patient from whom the tumor was obtained. HSCs can be used to reconstruct the immune system ( Figure 1D), both autologous and allogeneic HSCs can be used, since the collection of HSCs from a cancer patient may be limited [98]. Transplanted CD34 + HSCs develop into a complex human immune system without the risk of a graft-versus-host reaction (GVHR), since thymus education of human T-cells occurs in the context of mouse MHC molecules [99].…”

Section: Patient-derived Xenograft Modelsmentioning

confidence: 99%

“…In addition, the administrated PBMCs generate stable GVHR [107]. In order to support the engraftment of transplanted cells, animals expressing proteins of the human immune system have been developed on the basis of NSG mouse models [98]. For example, NSG-SGM3 mice express human IL3, granulocyte macrophage colony stimulating factor (GM-CSF), and stem cell factor (SCF), which allows stable engraftment of human HSCs.…”

Section: Patient-derived Xenograft Modelsmentioning

confidence: 99%

Mouse Tumor Models for Advanced Cancer Immunotherapy

Chulpanova

Kitaeva

Rutland

et al. 2020

IJMS

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Recent advances in the development of new methods of cancer immunotherapy require the production of complex cancer animal models that reliably reflect the complexity of the tumor and its microenvironment. Mice are good animals to create tumor models because they are low cost, have a short reproductive cycle, exhibit high tumor growth rates, and can be easily genetically modified. However, the obvious problem of these models is the high failure rate observed in human clinical trials after promising results obtained in mouse models. In order to increase the reliability of the results obtained in mice, the tumor model should reflect the heterogeneity of the tumor, contain components of the tumor microenvironment, in particular immune cells, to which the action of immunotherapeutic drugs are directed. This review discusses the current immunocompetent and immunocompromised mouse models of human tumors that are used to evaluate the effectiveness of immunotherapeutic agents, in particular chimeric antigen receptor (CAR) T-cells and immune checkpoint inhibitors.

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“…Humanized mice are commercially available, but many laboratories also produce their own mice for research needs. Some experimental protocols are also published for creating these mice [64][65][66]. Briefly, the two major choices for creating these mice that reflect the performance of the model in immuno-oncology research are the immune cells used to engraft the mice and the mouse strain used as a host for engraftment, which are discussed in the following paragraphs.…”

Section: Human Immune Cell Engrafted Mouse Modelsmentioning

confidence: 99%

Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development

Kähkönen¹,

Halleen²,

Bernoulli

2020

Cancers

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Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.

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Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology

Cited by 55 publications

References 20 publications

Targeted Transdermal Delivery of Curcumin for Breast Cancer Prevention

Targeted Transdermal Delivery of Curcumin for Breast Cancer Prevention

Mouse Tumor Models for Advanced Cancer Immunotherapy

Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development

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