Animal Models for the Development of Cancer Immunotherapy (eBook, ePUB)

Redaktion: Tan, Seng-Lai

• Format: ePub

Produktbeschreibung

Animal Models for the Development of Cancer Immunotherapy Provides readers with a clear understanding of the value and challenges of using common and emerging preclinical models in cancer immunotherapy research and development. Animal models are essential tools for studying a range of issues in preclinical and clinical research on therapies targeting cancerous tumors. As clinical trials of advances in cancer immunotherapy are predicted to outpace preclinical research in the near future, there remains an urgent need to develop better animal models for preclinical evaluation of novel modulators. Animal Models for the Development of Cancer Immunotherapy provides a detailed overview of different preclinical model systems for development of novel cancer immunotherapies while highlighting how key aspects of individual models translate into clinical findings. Covering the introduction, development, and therapeutic applications of animal models for cancer immunotherapy, this comprehensive volume helps pharmacologists identify suitable animal models, design pharmacological or translational studies, and advance their mechanistic understanding of therapeutic agents, and increase the possibility of success for novel immunotherapies in clinical settings. Chapters written by prominent leaders in the field address specific models that evaluate immuno-oncology drugs are supported by in-depth case studies and extensive references throughout. * Emphasizes the importance of modeling tumor metastasis in preclinical models for efficient translation of findings into the clinic * Explores recently discovered mechanisms of resistance and their preclinical modeling * Highlights the unique characteristics and features of autologous and allogeneic approaches for humanization of mouse models * Reviews development of bone marrow-liver-thymus (BLT) immune humanized mice and emerging alternative models such as genetically engineered mouse models (GEMM) * Discusses alternative animal models for cancer research such as severe combined immunodeficiency (SCID) pigs Animal Models for the Development of Cancer Immunotherapy is an essential resource for scientists and researchers in the pharmaceutical and biotechnology industries, medicinal chemists and biochemists, cell and molecular biologists, pharmacologists, immunologists, and clinicians.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 320
• Erscheinungstermin: 8. August 2022
• Englisch
• ISBN-13: 9781119535317
• Artikelnr.: 65464199

Autorenporträt

Seng-Lai Tan, PhD, is Chief Scientific Officer at Immunitas Therapeutics. He has more than 20 years of drug discovery and development experience in both small and large molecule therapeutic modalities, including multi-specific antibodies and stapled peptides. He is former Head of Immunology at Marengo (Elstar) Therapeutics and Forma Therapeutics, and has held leadership positions at EMD Serono Research & Development Institute and Roche.

Inhaltsangabe

List of Contributors xiii

Introduction 1
Mithun Khattar and Karuppiah Kannan

Tumor 3

Host 5

Modality 7

References 9

1 Transplantable Syngeneic Murine Tumor Models 11
Rich Woessner, Alexandra Borodovsky, Kris Sachsenmeier, Felix Scheuplein, Robert W. Wilkinson, Chaoyang Ye and Simon Dovedi

1.1 Introduction 11

1.2 Overview of Syngeneic Murine Tumor Models 14

1.2.1 Immunological Diversity in Syngeneic Models 14

1.2.2 Technical and Experimental Design Considerations 24

1.2.2.1 Timeline of Immune Response 24

1.2.2.2 Lab to Lab Variations 25

1.2.2.3 Housing and Husbandry Conditions 25

1.2.2.4 Age and Source of Mice 25

1.2.2.5 Microbiome Effects 26

1.2.2.6 Checkpoint Antibodies 26

1.2.2.7 Site of Implantation 27

1.3 Modeling the Immune Suppressive Tumor Microenvironment with Syngeneic Models 28

1.3.1 Immune Suppressive Metabolites 28

1.3.2 Immune Suppressive Cell Populations 30

1.3.2.1 Myeloid-Derived Suppressor Cells 31

1.3.2.2 Tumor-Associated Macrophages 32

1.3.2.3 Regulatory T Cells 33

1.3.2.4 Regulatory B Cells 34

1.3.2.5 Concluding Remarks 34

1.4 Genomic Analysis/Bioinformatics for Syngeneic Tumor Models 35

1.4.1 Background 35

1.4.2 Traditional Methods 35

1.4.2.1 Immunohistochemistry and Immunofluorescence 35

1.4.2.2 In Silico Imputation 37

1.4.3 Medium throughput methods 38

1.4.4 High-Throughput Methods: scRNAseq 38

1.4.5 Multi-omics Methods 39

1.4.6 Data Analysis 39

1.4.7 Technical and Sample Considerations 40

1.4.8 Challenges and Translation into Clinic 40

1.5 OT-1 Systems and OVA Expressing Tumor Models for Understanding the Effect of Immuno-Oncology (I-O) Agents on T-Cell Responses 41

1.6 Modeling Chemotherapy/Radiation Therapy + Immunotherapy Combinations with Syngeneic Models 43

1.6.1 Preclinical Modeling of Radiotherapy/Immunotherapy Combinations 44

1.6.2 Preclinical Modeling of Chemotherapy/Immunotherapy Combinations 45

1.6.3 Summary 46

1.7 Conclusions 46

References 48

2 Genetically Engineered Mouse Models (GEMMs) in Cancer Immunotherapy R&D
Zhao Chen 63

2.1 Current Challenges in Immuno-oncology In vivo Modeling 63

2.2 Pros and Cons of GEMM in Immuno-oncology Studies 67

2.3 Organoid-Based GEMM Tumors 68

2.4 Modeling Different TME Using GEMM 70

2.5 In vivo Target ID Based on GEMM 71

2.6 Modeling Immune System Functions with GEMM 71

References 72

3 Mouse Tumor Homografts Recapitulate Human Molecular Pathogenesis 75
Rajendra Kumari, Davy Ouyang and Henry Li

3.1 Introduction 75

3.2 Transplanted Syngeneic Cell Line Models 76

3.3 Spontaneous Autochthonous Mouse Models 78

3.4 Mouse-Derived Tumor Homografts 81

3.5 Generation of Tumor Homografts 83

Protocol 83

3.6 Orthotopic Implantation 87

3.7 Pancreatic Cancer Homografts 88

3.8 Prostate Cancer Homografts 94

3.9 Large Scale Mouse Clinical Trial Using Homografts 99

3.10 Limitations with Regard to Usage of Murine Tumor Homografts 101

3.11 Summary 101

Acknowledgments 102

References 102

4 Modeling Resistance to Immune Checkpoint Blockade 107
Michael Quigley, Matthew J. Meyer and Kanstantsin Katlinski

4.1 Introduction 107

4.2 The Use of Preclinical Mouse Models to Understand Mechanisms o