Tumor Immunology Molecularly Defined Antigens and Clinical Applications 1st Edition by Giorgio Parmiani 0415272165 9780415272162

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ISBN 10: 0415272165

ISBN 13: 9780415272162

Author: Giorgio Parmiani

Recent advances in immunology and molecular biology have resulted in new therapeutic approaches being generated and implemented in cancer clinics. The discovery of new antigens, mechanisms of antigen presentation, and interplay of cells involved in anti-tumor immunity have made the clinical control of some cancers more plausible than previously tho

Tumor Immunology Molecularly Defined Antigens and Clinical Applications 1st Table of contents:

1 Immune Recognition of Cancer – Tumor Antigens

Tumor antigens

Introduction

Cancer-Testis Antigens

Differentiation Antigens

Widely Expressed Proteins

Tumor-Specific Antigens

Class II MHC Restricted Tumor Antigens

Identification of Epitopes on Candidate Antigens

Modulation of T Cell Recognition

T Cell Receptor Analysis

Clinical Applications

References

2 Processing and Presentation of Antigen for the Activation of Lymphocytes to Tumor Cells

Antigen Processing and Presentation are Critical Components of Lymphocyte Activation and Targeting

Antigen Processing and Presentation

Endogenous Pathway of Antigen Processing and Presentation

Exogenous Pathway of Antigen Processing and Presentation

Antigen Presentation Molecules

MHC Class I Molecules Preferentially Present Endogenously Synthesized Peptide Antigens to CD8+ T CELLS

MHC Class II Molecules Preferentially Present Exogenously Synthesized Peptide Antigens

The Role of the MHC-Encoded Class I-Like (MHC Class IB) Molecules is Unknown

CD1 Molecules Present Lipid Antigens

Heat Shock Proteins are Carriers for a Wide Repertoire of Peptides

Antigen Presentation by Professional Antigen Presenting Cells

Dendritic Cells

Antigen Uptake by Dendritic Cells

Dendritic Cells Maturation and Migration

Dendritic Cell-Mediated Activation of B Cells and T cells within The Lymph Nodes

Cross-Priming or Indirect Antigen Presentation for Activating T Lymphocytes

Generating Dendritic Cells in Vitro for Immunization/Vaccination Therapies

Macrophages/Monocytes

B Lymphocytes

Non-Professional Antigen Presentation by Tumor Cells

Activation of CD8+ T Lymphocytes

Activation of CD4+T Lymphocytes

Conclusions

Acknowledgments

References

3 Cellular Recognition of Tumors by T and NK Cells

Basis for T Cell Recognition of Tumors

Role of T Cells in Antitumor Responses

CD4+T Lymphocytes and Cancer

Direct vs. Indirect Antigen Presentation IN CD4+-MEDIATED IMMUNE RESPONSE

Why The Helper Arm of the Immune Response to Tumors May be Defective

Both TH1 and TH2 CD4+T Cells can Cooperate in Antitumor Responses

CD4+T Lymphocytes and Human Cancer

CD8+T Lymphocytes and Cancer

CD8+T Cells in Human Cancer

Why CD8+-Mediated T Cell Responses may Fail to take Place Even When Tumors are Antigenic

Direct vs. Indirect Antigen Presentation in CD8+-Mediated Anti-Tumor Responses

Role of Natural Killer Lymphocytes

The Basis for NK Cell Recognition of Tumors

NKT Cells

Circulation and Homing of Tumor-Specific T and NK Cells, and the Role of Homing-Associated Adhesion Molecules and of Chemokines

References

4 Humoral Recognition of Cancer

Mechanisms for B Cell Recognition of Tumor Antigens and for Effector Actions

Target Cancer Antigens

The Basis for Antibody-Mediated Therapy of Cancer

Construction of Cancer Vaccines that Augment the Antibody Response

Vaccines Against Gangliosides

Vaccines Against Other Antigens and Polyvalent Vaccines

Preparation of Monoclonal Antibodies that Recognize Cancer

Therapy with Monoclonal Antibodies

Diagnostic Applications of Monoclonal Antibodies

Conclusion

References

5 Immunotherapy of Cancer

Introduction

Some General Principles

Differences in Therapeutic versus Preventive Vaccines

Reduce Tumor Bulk and Immunize away from the Tumor

Switching Immune Responses from TH2 to TH1 and Cell Mediated Responses

Select Antigens Expressed at High Density on Tumor Cells Which Have High Numbers of Precursor T Cells Against Them

“Helper” Molecules are Needed to Generate Optimal Immune Responses

Selecting the Right Adjuvants

Tumor Antigens Recognized by the Immune System of Humans

Antigens Recognized by T Cells

Vaccine Delivery Systems for Generation of Immune Responses Against Tumors

Whole Cells and Cell Fragments

Cytokine Gene Transfected Cancer Cells

Proteins and Peptides as Vaccines

Viral Vectors

“Naked” DNA Vaccines

Dendritic Cells

Conclusions

Cytokine Therapy

Francesco M. Marincola

Interferons

Interleukin-2

Adoptive Therapy and Interleukin-2

Tumor Antigens and Interleukin-2

Chemotherapy and Interleukin-2

Other Cytokines

Combination Treatments with Interleukin-2

Conclusions

Adoptive Immunotherapy

Francesco M. Marincola

Introduction

Lak and TILs as Effectors of Adoptive Immunotherapy

Adoptive Immunotherapy with TIL in Melanoma Patients

TILs Specificity and the Antigenic Heterogeneity of Target Cells

Identification of Relevant Epitopes Recognized by TIL

In vitro Selection and Expansion of Antigen-specific TIL

Adoptive Immunotherapy in Hematological Diseases

Conclusions

References

6 Tumor Evasion of Immune System

Introduction

Modification of Tumor Cells that Induce Immunologic Ignorance

Evasion by MHC Altered Gene and Cell Surface Expression

Altered MHC Class I Antigen Presentation

Structural Defects of β2-Micro globulin Gene

Abnormalities that Affect Class I MHC Heavy Chain

Modulation of MHC Class 1 Expression by Viral Infection

Loss of Tumor Antigen Expression

Immunoselection of Mutated Peptides that Evade Antigen Presentation

Expression of Molecules that Inhibit T and Nk Response

Immunosuppression Induced by Tumor Cells

Immunosuppressive Cytokines

Expression of Molecules that Operate on the Apo-Fas Pathway

Abnormalities in Signal Transduction of T Cells

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