Cancer Immunology (2015) | ПРЕЦИЗИОННАЯ ОНКОЛОГИЯ

Cancer immunology. Bench to bedside immunotherapy of cancers (2015)

Cancer immunology. Bench to bedside immunotherapy of cancersNima Rezaei (Ed.). Springer-Verlag (2015)


Frontiers in cancer immunotherapy »

  • Introduction
  • Innate cells as initiators of the adaptive immune response
  • Cellular immunotherapy
  • Active and passive immunotherapy
    • Active immunotherapy
    • Nonspecific immunotherapy
  • Stimulation of responses in vivo
  • Adoptive immunotherapy
  • Cancer vaccines
    • Dendritic cells
    • Physical barriers, tumor stroma and vessels
  • Mechanisms of tumor-induced tolerance/escape from the immune system
    • Treg cells
    • Myeloid-derived suppressor cells
    • Macrophages
  • Candidates for immunotherapy in oncology
  • Combination immunotherapy
    • Chemotherapy and mAb
    • Chemotherapy and active specific immunotherapy
    • Chemotherapy and adoptive lymphocyte immunotherapy
    • Immunotherapy with radiation therapy
  • Humoral immunotherapy
  • Concluding remarks
  • References

Novel strategy of cancer immunotherapy: spiraling up »

  • Introduction
  • Natural Killer cells: the key effectors of innate immunity
  • Adoptive IL-2/LAK (or CIK) therapy of cancer
  • Tumor-infiltrating lymphocytes (TILs) in cancer immunotherapy
  • Autologic vaccines on the base of dendritic cells (DC vaccines)
  • Advantages of combined implication of DC vaccines and activated lymphocytes
  • Spiral up
  • Concluding remarks
  • References

Novel prognostic biomarkers for personalized cancer treatment »

  • Introduction
  • Presentation
  • New biomarkers for the treatment of tumors
  • Guidelines for the identifications of “suitable” biomarkers: a healthy longevity is linked to an healthy function of the immune system. the pathology is generated by alterations of this system
  • The importance of the evaluation of both genders as independent groups
  • Men and women follow different strategies to regulate the homeostasis of the immune system
    • Variations of pro- and anti-inflammatory cytokine levels regulate the immune response and could influence the healthy state
    • “Double prognostic biomarkers”: appropriate variations between proand anti-inflammatory cytokines assure the success of the immune response but following different gender pathways
    • The efficiency of the treatment is related to a reestablishment of IL-6 pathways in women, and IFN-γ pathways in men
  • The valuation of the thioredoxin and CD30 systems for the prognostic, diagnostic, and therapeutic stratification of patients
    • Trx1/RTx1 system
    • The CD30/CD30L/sCD30 system
  • New “double biomarkers” that are prognostic for patient stratification and for the personalized therapies
  • Concluding remarks
  • References

Tumor antigen and epitope identification for preclinical and clinical evaluation »

  • Introduction
  • Reverse immunology approach to peptide identification
    • Target antigen identification
    • In silico peptide predictions
    • Epitope validation
  • Direct immunology approach
    • Isolation of peptide–MHC complexes
    • Analysis and sequencing of MHC-associated peptides
  • Human immunotherapy against tumor-associated peptides
  • Strategies to enhance the immunogenicity of peptide epitopes
    • Potential adjuvants for boosting immune responses
    • TLR agonists in cancer vaccine trials
  • Future prospects
  • Concluding remarks
  • References

Strategies to target tumor immunosuppression »

  • Introduction
  • The balance is tilted: mechanisms of tumor immune escape
  • Tolerance mechanisms
  • Immunosuppression mechanisms
    • Shifting the balance: strategies to target tumor immunosuppression
  • Strategies targeting homing of effector T cells
  • Strategies targeting the activity of effector T cells
    • Concluding remarks
    • References

Overcoming cancer tolerance with immune checkpoint blockade »

  • Introduction
  • Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4): a paradigm for immune checkpoint blockade
    • CTLA-4 function
    • Preclinical development of CTLA-4 blocking therapy
    • CTLA-4 blockade monotherapy in melanoma
    • Toxicity
    • Immune-related response criteria
    • CTLA-4 blockade in cancers other than cutaneous melanoma
    • CTLA-4 blockade as combination therapy
  • Programmed death 1 (PD-1) pathway
    • Function
    • PD-1 pathway in cancer
    • PD-1 blockade
    • PD-L1 Blockade
  • Combination immunotherapy
    • CTLA-4 blockade and vaccination
    • CTLA-4 blockade and cytokine therapy
    • Combination checkpoint blockade
  • Other checkpoint pathways under development
    • Lymphocyte Activation Gene-3 (LAG-3)
    • 4-1BB
    • OX-40
    • Glucocorticoid-Induced TNFR Related Protein (GITR)
    • CD40
    • TGN1421: a cautionary tale
  • Concluding remarks
  • References

Gene therapy and virus-based cancer vaccines »

  • Introduction
  • Viral vectors used in cancer gene therapy
    • Retrovirus vectors (RVVs)
    • Poxvirus vectors (PVVs)
    • Adenoviral vectors (AdVVs)
    • Adeno-associated virus vector (AAVVs)
    • Herpes simplex virus type 1 vectors (HSVVs)
  • Non-viral methods of gene delivery
    • Delivery of plasmid DNA
  • Cancer gene therapy
    • Oncogene and tumor suppressor gene targeted gene therapy
    • Enhancing pro-drug cytotoxicity in the tumor cells through gene therapy
    • Thymidine kinase (TK)
    • Cytosine deaminase (CD)
  • Anti-angiogenesis gene therapy
  • Cancer vaccines and vaccine production
    • Virus-based vaccines
  • Oncolytic Viruses
    • Mechanism of action
    • Viral agents used as oncolytic agents
  • Concluding remarks
  • References

Cancer stem cells: biology and potential therapeutic applications »

Immunologic approaches to targeting cancer stem cells »

  • Introduction
  • ALDEFLUOR+/ALDHhigh serves as a specific marker for cancer stem cells in multiple tumor types
  • Cancer stem cells are resistant to conventional tumor therapies
  • Innate immune response to cancer stem cells
  • Cancer stem cell-primed t cells specifically targeting cancer stem cells
  • Development of cancer stem cell-specific vaccine in immunocompetent host
  • Targeting the tumor microenvironment as a strategy to enhance immunological targeting of cancer stem cells
  • Concluding remarks
  • References

Hematopoietic stem cell transplantation and lymphodepletion for the treatment of cancer »

  • Introduction
  • Hematopoietic stem cell transplantation (HSCT)
    • Sources of hematopoietic stem cells (HSCs)
    • Autologous and allogeneic HSCT
    • Graft-versus-host disease and the graft versus tumor effect
    • Myeloablative effects that promote the elimination of hematologic malignancies
    • Non-myeloablative conditioning
  • Lymphodepletion for the treatment of solid tumors
    • Lymphodepletion-induced T cell thymopoiesis is important for reconstitution of the T cell repertoire
    • Lymphodepletion-induced homeostatic proliferation as strategy to augment antitumor immunity
    • Use of animal models to address immunological effects of lymphodepletion
  • Concluding remarks
  • References

Combination of chemotherapy and cytokine therapy in treatment of cancers »

  • Introduction
  • Immune response in the control of cancer
    • Cancer immunoediting theory
    • Tumors escape from the host immune response
  • Immunotherapy of cancer
    • Enhancing antitumor immunity using cytokines
  • Overcoming tumor resistance and the use of chemotherapeutic agents
    • Chemotherapy plus immunotherapy
    • Rationale for drug selection
  • Combined therapies
    • Preclinical experience
    • What have we learned from the clinical practice?
  • Concluding remarks

T cell immunotherapy: from synthetic biology to clinical practice »

  • Introduction
  • T cell responses to cancer
  • From polyclonal to single-specificity effector T cells
  • From MHC to antibody-based recognition: therapy with T cells expressing CARs
    • History of CAR development
    • Inclusion of T cell signaling moieties
    • Vectors used for CAR expression
    • Impact of T cell culture and expansion techniques
    • Clinical advances  with CAR Therapy
  • Concluding remarks
  • References

Role of γδ T lymphocytes in cancer immunosurveillance and immunotherapy »

  • Introduction
  • TCRγδ repertoires and functions
    • Mouse γδ T-cell subsets
    • Human γδ T-cell subsets
  • γδ T-cell activation: TCRγδ agonists
    • Phosphoagonists (phosphoantigens)
    • Aminobisphosphonates
    • Alkylamines
    • Protein ligands
  • γδ T-cell activation: costimulatory molecules
    • CD27
    • CD28
    • Fc Receptors: CD16
  • γδ T-cell activation via natural killer receptors (NKRs)
    • NKG2D
    • NKG2A
    • Natural cytotoxicity receptors (NCRs)
    • DNAM-1
  • Tumor cell recognition by γδ T Cells: TCRs versus NKRs
  • γδ T-cell responses to tumors
    • Antitumor properties
    • Pro-tumor properties
  • γδ T-cell modulation in cancer clinical trials
  • Concluding remarks
  • References

Adoptive T-cell therapy: optimizing chemokine receptor-mediated homing of T cells in cancer immunotherapy »

  • Introduction
  • History of adoptive immunotherapy of malignancy
  • T-cell infiltration correlates with prognosis
  • Adoptive T-cell therapy
  • Challenges in adoptive T-cell therapy
  • Chemokines
  • The role of chemokines in directing tissue trafficking in tumors
  • Overexpression of chemokine receptors in engineered lymphocytes to be used for cancer immunotherapy
  • Concluding remarks
  • References

B cell regulation of antitumor response »

  • Introduction
  • Mechanisms underlying B cell modulation of antitumor immune response
  • B cells and the role of Tregs
  • B-regulatory cell infiltration into human tumors
  • Breg function in non-Hodgkin lymphoma
  • Effects of depletion of B cells on antitumor immunity
  • Concluding remarks
  • References

Monoclonal antibodies for cancer immunotherapy »

  • Introduction
  • Structural and functional features of antibodies
  • Natural antibodies in cancer
  • Finding an appropriate antibody target for cancer therapy
    • Characteristics of a favorable cell surface antigen
    • Classification of cancer antigens
    • Target identification approaches
  • Molecular mechanisms involved in monoclonal antibody-based therapy
    • Direct tumor cell elimination
    • Harnessing the potential capacity of immune system to eliminate tumors
    • Targeting tumor stroma and vasculature
  • Engineered antibodies
    • Murine monoclonal antibodies
    • Chimeric and humanized monoclonal antibodies
    • Fully human monoclonal antibodies
    • Antibody fragments
    • Bispecific antibodies (BsAbs)
    • Antibody fusion constructs
    • Improvement of antibody function
  • Evaluation of antibody efficacy
    • Preclinical evaluations
    • Clinical evaluations
  • Clinically-approved monoclonal antibodies
    • Trastuzumab
    • Bevacizumab
    • Rituximab
    • Therapeutic monoclonal antibodies approved by non-FDA organizations
  • Monoclonal antibodies currently undergoing clinical trials
  • Combinational monoclonal antibody-based modalities
    • Combination with chemotherapy
    • Combination with radiotherapy
    • Combination with other immunotherapeutic methods
    • Other combinational approaches
  • Current limitations in monoclonal antibody-based therapies
    • Tumor escape
    • Relatively low single agent activity
    • Low tissue penetration
    • Fc-Fc receptor interactions and associated limitations
    • High production cost
  • Concluding remarks
  • References

Toll-like receptor pathway and its targeting in treatment of cancers »

  • Introduction
  • TLRs play important roles in human carcinogenesis
  • TLR regulates tumor-induced immune system response
  • TLR targeting may inhibit cancer cell proliferation
  • TLR triggering can promote antitumor response
  • Regulatory effects of TLRs on PI3K/Akt signaling controlling tumor progression
  • TLR-mediated hypoxia-inducible factor 1 (HIF-1) expression leads to tumor progression
  • Role of TLRs in tumor cell lysis and apoptosis
  • TLRs are involved in tumor metastasis
  • Concluding remarks
  • References

Recent advances in the use of NK cells against cancer »

  • Introduction
  • NK cell basics
    • How do NK cells become activated to kill?
    • Why should NK cells be targeted as anticancer agents?
  • Challenges involved in targeting NK cells
    • How many NK cells are in cancer patients and tumors?
    • What is the functionality of NK cells in tumors?
  • Cancer immunotherapies involving NK Cells
  • Adoptive NK cell transfer
    • How can we produce large numbers of activated NK cells?
  • Autologous transfer of NK cells
  • Allogeneic transfer of NK cells
  • NK cell lines for allogeneic adoptive transfer
  • NK cells, ADCC, and mAb therapy
  • Cytokines and promoting NK activation/stopping inhibition
  • Concluding remarks
  • References

Dendritic cell vaccines for cancer therapy: fundamentals and clinical trials »

  • Introduction
  • Strategies for developing clinical grade DC vaccines
  • Routes of administration
  • DC vaccine for prostatic cancer
  • DC vaccine for melanoma
  • DC vaccine for colorectal cancer
  • DC vaccine for nervous tissue cancer
  • Concluding remarks
  • References

Tumor-associated macrophages and cancer development »

  • Introduction
  • Cancer and inflammation
  • Development of myeloid lineage cells including macrophages
  • Characteristics of TAMs
  • “Reeducating” TAMs to cytotoxic phenotype
  • Concluding remarks
  • References

Photodynamic therapy and antitumor immune response »

  • Introduction
  • Photodynamic therapy
  • Closer look up at the PDT and triggered immune response
  • Significance of PDT and adaptive immunity
  • Mechanism of PDT immunologic effects
  • Case studies
  • Concluding remarks
  • References

Polarization of tumor milieu: therapeutic implications »

  • Introduction
  • Recruitment of inflammatory cells by cancer cells
  • Macrophage plasticity: M1 and M2 phenotypes
  • TAM: cells with M2 phenotype
  • M1 → M2 tumor microenvironment reversal: therapeutic approach
  • Concluding remarks
  • References

Immunotherapies targeting a tumor-associated antigen, 5T4 oncofetal glycoprotein »

  • Introduction
    • 5T4 trophoblast glycoprotein is an oncofetal antigen
  • 5T4 and epithelial mesenchymal transition (EMT)
  • 5T4 Modulation of chemokine and Wnt signaling pathways
  • Vaccines
    • Preclinical studies
    • Early-phase clinical trials of MVA-h5T4 (TroVax)
    • TroVax phase III clinical trial in RCC
    • Insights from the 5T4 KO mouse
    • Improving vaccine regimens
  • 5T4 antibody-targeted superantigen therapy
    • Preclinical studies
    • Early-phase clinical studies
    • A phase II/III Clinical Trial in RCC
  • Other 5T4 antibody-targeted therapies
    • Antibody-drug conjugates (ADC)
    • Direct 5T4 antibody effects
    • 5T4 chimeric antigen receptors
  • Concluding remarks
  • References

Emerging biomarkers during clinical development of anti-CTLA4 antibody therapy »

  • Introduction
  • Absolute lymphocyte count
  • Analyses of different cell populations in peripheral blood
    • T cell activation markers
    • Regulatory T cells
    • Myeloid-derived suppressor cells (MDSCs)
  • Antigen-specific immunological monitoring
    • Antigen-specific antibody response
    • Antigen-specific T cell response
  • Analyses of specific T cell populations in the tumor microenvironment
  • Future perspectives
  • Concluding remarks
  • References

New advances in radioimmunotherapy for the treatment of cancers »

  • Introduction
  • Principles of radioimmunotherapy
  • Radionuclides and radiolabeling techniques for therapy
    • Radionuclides
    • Labeling techniques
  • The treatment of B cell lymphoma with anti-CD20 antibodies
  • Promising results in hemopathies using other antibodies
    • Targeting of lymphoma with anti-CD22 antibodies
    • Targeting of multiple myeloma using anti-CD138 antibodies
  • RIT of metastatic prostate cancer
  • RIT with α-emitting radionuclides
    • Therapeutic indication
    • Limited availability
    • Issues and current developments
  • High efficacy of pretargeting approaches in metastatic thyroid carcinoma
  • Immuno-PET: the future for dosimetry assessment and patient selection
    • Immuno-PET and development of new drugs
    • Patient selection for therapy
    • Determination of the cumulated activity concentration for RIT
    • Therapy response
  • Concluding remarks
  • References

Psychoneuroendocrinoimmunotherapy of cancer »

  • Introduction
  • The physiopathology of anticancer immunity
  • The fundamental phases of tumor onset and dissemination
  • Main cancer-related immunoneuroendocrine alterations
  • Preliminary clinically applied PNEI strategies
  • Future perspectives
  • Concluding remarks
  • References

Ethical considerations in cancer immunotherapy »

  • Introduction
  • Ethical issues in immunotherapy of cancer
  • Unique toxicities
  • Evaluation of efficacy in the clinical trial and non-research settings
  • Ethical justification for initiation of treatment in individual patients
  • Concluding remarks
  • References

 

0