Translational Immunotherapy of Brain Tumors

Translational Immunotherapy of Brain Tumors

1st Edition - February 6, 2017

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  • Editor: John H. Sampson
  • Hardcover ISBN: 9780128024201
  • eBook ISBN: 9780128026250

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Translational Immunotherapy of Brain Tumors gives researchers and practitioners an up-to-date and comprehensive overview of the field. Chapters include adoptive immunotherapy, immunosuppression, CAR therapy of brain tumors, and dendritic cell therapy for brain tumors. Very few agents have been shown to be efficacious in the treatment of malignant gliomas. Recently, there have been a number of studies demonstrating the potential success of immunotherapy for brain tumors. Immunotherapeutics are becoming the most frequent drugs to be used in cancer therapy. These new breakthroughs, now approved by the FDA, are a part of multiple phase III international trials and ongoing research in malignant glioma, meaning that the information in this cutting-edge book will be of great importance to practitioners and researchers alike. 2018 BMA Medical Book Awards Highly Commended in Oncology

Key Features

  • Comprehensive overview, providing an update on immunology, translational immunotherapy, and clinical trials relating to malignant gliomas
  • Edited by a prominent neurosurgeon with contributions by leading researchers in the field
  • Ideal resource for researchers and practitioners interested in learning about mechanisms that use the immune system to treat brain tumors


Researchers and practitioners in the fields of neuroscience, neurology, neurooncology, and neurosurgery

Table of Contents

  • Section I. Immunological Features of Brain Tumors

    Chapter 1. An Introduction to Immunotherapy in the Treatment of Brain Tumors

    • Introduction
    • The Immune Response
    • Immune Tolerance
    • Unique Aspects of the Central Nervous System Immune Response
    • Cancer Immunotherapies

    Chapter 2. Immune Constitution of Patients With Brain Tumors

    • Background and Discovery
    • Current Understanding: Analyzing Systemic Immune Dysfunction
    • Current Understanding: Analyzing the Tumor
    • Clinical Opportunities
    • Conclusion

    Chapter 3. The Role of Regulatory T Cells and Indoleamine-2,3-dioxygenase in Brain Tumor Immunosuppression

    • Background and Discovery
    • Origin of Tregs
    • Function of Tregs
    • Tregs in the Cancer Immunity Cycle
    • Tregs and Glioma
    • Tryptophan Catabolism in Immunity and in Cancer
    • IDO1, IDO2, and TDO
    • The AhR
    • Mechanisms of Immune Regulation by the IDO Pathway
    • The IDO Pathway in Cancer and in Glioma
    • Targeting Tregs in Preclinical Model
    • Targeting IDO in Preclinical Models
    • Clinical Trial Data
    • Conclusion

    Chapter 4. The Role of Myeloid-Derived Suppressor Cells in Immunosuppression in Brain Tumors

    • Background and Discovery of the Myeloid Cell
    • Preclinical Data: Targeting the MDSC Population
    • Clinical Approaches to Targeting MDSCs

    Chapter 5. Tumor-Specific Mutations in Gliomas and Their Implications for Immunotherapy

    • Introduction
    • Mutations as Immunotherapeutic Targets
    • Isocitrate Dehydrogenase 1 Mutations in Gliomas
    • IDH1 Mutations as an Immunotherapeutic Target
    • Preclinical Investigations: IDH1-R132H Peptide Vaccines
    • Clinical Investigations: IDH1-R132H Peptide Vaccines
    • Roadblocks and Future Directions for Targeting IDH1 Mutations
    • Epidermal Growth Factor Receptor and Variant III in Gliomas
    • EGFR Mutations as an Immunotherapeutic Vaccination Target
    • Preclinical Investigations: EGFRvIII Vaccination
    • Clinical Investigations: EGFRvIII Vaccination
    • Roadblocks for Targeting EGFRvIII
    • Histone Mutation Background
    • Histone Mutations in Pediatric Gliomas
    • H3.3 Mutations as an Immunotherapeutic Target
    • Roadblocks and Future Directions for Targeting H3 Mutations

    Section II. Studying Brain Tumor Immunotherapy

    Chapter 6. Preclinical Immunotherapeutic Animal Models for Brain Tumors

    • Introduction
    • Spontaneous and Experimentally-Induced Autochthonous Brain Tumor Animal Models
    • Syngeneic Transplantation Brain Tumor Models
    • Genetically Engineered Mouse Models
    • Xenograft Models of Glioblastoma
    • Humanized Mouse Models
    • Conclusion

    Chapter 7. Imaging Studies in Immunotherapy

    • Clinical Considerations
    • Advanced Imaging Assessments
    • Conclusion

    Chapter 8. Immunotherapy Clinical Trials in Neuro-Oncology

    • Introduction
    • Early Immunotherapy
    • Immunotherapy in the 21st Century
    • Checkpoint Inhibitors
    • Therapeutic Cancer Vaccines
    • Chimeric Antigen Receptor T Cells
    • Viral Therapy in Solid Tumors
    • Bispecific T Cell Engagers
    • Immunotherapy Clinical Trial Design in Neuro-Oncology
    • Study Design
    • Assessing the Candidate
    • Assessment of Safety
    • Assessment of Response

    Section III. Experimental Brain Tumor Immunotherapies

    Chapter 9. Peptide-Specific Vaccines

    • Background and Discovery
    • Preclinical Data and Principles of Peptide Vaccines
    • Clinical Trial Data
    • Wilms Tumor Peptide 1
    • Vaccination Targeting IDH-1R132H
    • Multipeptide Vaccination Regimens
    • Conclusion

    Chapter 10. Immunotoxin Therapy for Brain Tumors

    • Introduction
    • History of Immunotoxins
    • Immunotoxins for Brain Tumor Therapy
    • Future Directions
    • Conclusion

    Chapter 11. Checkpoint Blockade Immunotherapy for Glioblastoma: Progress and Challenges

    • The Tumor Immune Response and Immune Checkpoint Biology
    • Immune Checkpoints in Malignant Glioma
    • Immune Checkpoint Blockade
    • Feasibility of Checkpoint Blockade for Central Nervous System Malignancies
    • Clinical Progress of Checkpoint Blockade for Glioblastoma
    • Emerging Targets for Checkpoint Blockade
    • On the Horizon: Immunomodulatory Antibodies for T Cell Costimulation
    • Conclusion

    Chapter 12. Dendritic Cell Therapy for Brain Tumors

    • Introduction
    • Tumor Microenvironment
    • Dendritic Cells in Immunology
    • Dendritic Cell–Based Vaccine: Current Approaches
    • Antigen Targets
    • Routes of Administration
    • Safety and Complications
    • Immune Response
    • Clinical Response and Survival Benefits
    • Radiologic Findings
    • Clinical Trials
    • Future Directions
    • Conclusion

    Chapter 13. Adoptive Immunotherapy Against Brain Tumors

    • Introduction
    • Approaches

    Chapter 14. Chimeric Antigen Receptor Therapy of Brain Tumors

    • Chimeric Antigen Receptors Through the Generations
    • Success of Targeting Hematogenous Malignancies: CD19 Chimeric Antigen Receptors
    • Solid Tumors as a Chimeric Antigen Receptor Target
    • Chimeric Antigen Receptor Therapy for Brain Tumors
    • The Question of Delivery
    • Potential Challenges
    • Future Perspectives

Product details

  • No. of pages: 404
  • Language: English
  • Copyright: © Academic Press 2017
  • Published: February 6, 2017
  • Imprint: Academic Press
  • Hardcover ISBN: 9780128024201
  • eBook ISBN: 9780128026250

About the Editor

John H. Sampson

John H. Sampson
John H. Sampson, MD, PhD, MBA

Dr. Sampson is the Robert H. and Gloria Wilkins Distinguished Professor of Neurosurgery and Chair of the Department of Neurosurgery for the Duke University Medical Center. He holds a leadership role in the Duke Cancer Institute’s Neuro-Oncology Program and is a recognized leader in the surgical and experimental treatment of brain tumors with a focus on immunotherapy and drug delivery. He has authored more than 220 peer-reviewed publications in this field and serves on the Editorial Boards of the all the major journals in the field.

Dr. Sampson has received special training in the surgical resection of very complex brain tumors. In addition, he has special training in the design and conduct of clinical trials. He did his research training under the internationally renowned scientist, Darell D. Bigner, and Nobel Laureate, Gertrude Elion. He currently focuses his clinical practice on treating patients with both benign and malignant brain tumors and divides his time between his clinical practice and an active research laboratory investigating new modalities of direct brain tumor infusion and immunotherapy.

Dr. Sampson is internationally recognized in the field of neurosurgery and has received a number of national and international awards and grants in recognition of his expertise in neuro-oncology and especially in the area of immunotherapy for brain tumors. He developed a vaccine against a common mutation in brain tumors that was given Breakthrough Therapy Designation by the FDA after it was shown to extend survival in patients with the most malignant form of brain cancer. His work on another vaccine was also recently published in the journal Nature. His work has been highlighted on the CBS Evening News, 60 Minutes, The Wall Street Journal, and The Diane Rehm Show.

Affiliations and Expertise

Robert H. and Gloria Wilkins Professor of Neurosurgery, Chair, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA

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