Translational Immunotherapy of Brain Tumors

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-1^R132H
• 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