Preprint Review Version 1 This version is not peer-reviewed

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

Version 1 : Received: 30 April 2020 / Approved: 30 April 2020 / Online: 30 April 2020 (17:10:32 CEST)

A peer-reviewed article of this Preprint also exists.

Kähkönen, T.E.; Halleen, J.M.; Bernoulli, J. Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development. Cancers 2020, 12, 1615. Kähkönen, T.E.; Halleen, J.M.; Bernoulli, J. Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development. Cancers 2020, 12, 1615.

Journal reference: Cancers 2020, 12, 1615
DOI: 10.3390/cancers12061615

Abstract

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.

Subject Areas

humanized mice; human immune system; preclinical oncology model; metastasis model; immunotherapy; efficacy; safety

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