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A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research
Published on: August 15, 2019
Experimental animal modeling for immuno-oncology
Qi-Xiang Li1, Gerold Feuer2, Xuesong Ouyang3
1Crown Bioscience Inc., 3375 Scott Blvd, Suite 108, Santa Clara, CA 95054, USA; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
Abstract:
Immuno-oncology (I/O) research has intensified significantly in recent years due to the breakthrough development and the regulatory approval of several immune checkpoint inhibitors, leading to the rapid expansion of the new discovery of novel I/O therapies, new checkpoint inhibitors and beyond. However, many I/O questions remain unanswered, including why only certain subsets of patients respond to these treatments, who the responders would be, and how to expand patient response (the conversion of non-responders or maximizing response in partial responders). All of these require relevant I/O experimental systems, particularly relevant preclinical animal models. Compared to other oncology drug discovery, e.g. cytotoxic and targeted drugs, a lack of relevant animal models is a major obstacle in I/O drug discovery, and an urgent and unmet need. Despite the obvious importance, and the fact that much I/O research has been performed using many different animal models, there are few comprehensive and introductory reviews on this topic. This article attempts to review the efforts in development of a variety of such models, as well as their applications and limitations for readers new to the field, particularly those in the pharmaceutical industry.
Insights
Developing relevant animal models is crucial for advancing immuno-oncology (I/O) therapies. This review explores various I/O preclinical models, addressing key challenges in cancer immunotherapy drug discovery and patient response.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Immuno-oncology (I/O) has seen rapid advancements with immune checkpoint inhibitors.
- Significant questions remain regarding patient response variability and optimization.
- Effective preclinical models are essential for addressing these I/O challenges.
Purpose of the Study:
- To review the development of diverse preclinical animal models for I/O research.
- To discuss the applications and limitations of current I/O models.
- To provide an introductory overview for researchers new to the field, especially in the pharmaceutical industry.
Main Methods:
- Comprehensive literature review of existing immuno-oncology animal models.
- Analysis of model systems used in I/O drug discovery.
- Evaluation of model relevance for predicting clinical response.
Main Results:
- Identification of various preclinical models utilized in I/O research.
- Discussion of the strengths and weaknesses of different model systems.
- Highlighting the unmet need for more predictive I/O models.
Conclusions:
- A critical need exists for improved and relevant animal models in I/O drug discovery.
- Understanding model limitations is key to advancing novel cancer immunotherapies.
- This review serves as a guide to selecting and utilizing appropriate I/O preclinical models.
