This volume explores recent advances in understanding of fundamental immunology and insights into the dynamic interactions between tumors and the immune system, that provide new opportunities for therapeutic intervention in cancer. Chapter topics include evolving paradigms in the innate and adaptive response, newly appreciated immunosuppressive mechanisms, and novel preclinical strategies for manipulation of the immune system for therapeutic benefit in cancer. In addition, recent successes in the clinic, and emerging opportunities are covered. Future possibilities, such as the use of antibody engineering, fusion proteins, and the retargeting of immune cells through T-cell receptor engineering are discussed by leaders in the field, focusing on recent clinical experience, promising technologies, and challenges to clinical success.

Zusammenfassung

Recent advances in understanding of fundamental immunology have created new insights into the dynamic interactions between tumors and the immune system. This includes new understanding of T- and B-cell interaction, immune inhibitory mechanisms including the biology of T regulatory cells, myeloid suppressor cells, and dendritic cell subsets.

Enhanced understanding of mechanisms underlying T-cell anergy such as arginine deprivation, immunosuppressive cytokines, defective innate and interferon response pathways, and NKG2D downregulation have all provided new insight into suppression of anti-tumor immunity and tumor evasion.

In addition to emerging understanding of tumor evasion, new immune targets such as CTLA4 blockade, NK stimulatory receptors, manipulation of the antigen processing and presentation, cytokine and costimulatory responses all provide new possibilities for enhancing anti-tumor immunity even in tumors previously felt to be resistant to immune attack. Several of these strategies have already been realized in the clinic. The volume will explore evolving paradigms in antigen presentation, dendritic cell biology, the innate response and immunosuppressive mechanisms, and emerging strategies for manipulation of the immune system for therapeutic benefit that have realized success in neuroblastoma, leukemia, melanoma, lung cancer, and allogeneic transplantation. Early successes as well as failures will be highlighted to provide a snapshot of the state of clinical immunotherapy with an eye to future possibilities such as combination therapies, adoptive T-cell transfer, and the retargeting of immune cells via T-cell receptor engineering.

Inhalt

Contents

Part I Immune Activation, Suppression and Manipulation of the Immune Antitumor Response

Myeloid-Derived Suppressor Cells in Cancer.....Christos E. Kyriakopoulos, Alberto J. Montero, and Claudia Marcela Diaz-Montero

The Role of B Cells in Shaping the Antitumor Immune Response......Yu Zhang, Taylor H. Schreiber, and Joseph D. Rosenblatt

Heat-Shock Protein-Based Cancer Immunotherapy.....Taylor H. Schreiber

Activation of NK Cell Responses and Immunotherapy of Cancer......George J. Weiner

Induction of Tumor Immunity by Targeted Inhibition of Nonsense-Mediated mRNA Decay.....Eli Gilboa

Employing T Cell Homeostasis as an Antitumor Strategy.....Shawn M. Jensen, Christopher C. Paustain, and Bernard A. Fox

Adoptive Cell Therapy of Systemic Metastases Using erbB-2-Specific T Cells Redirected with a Chimeric Antibody-Based Receptor.....Dinorah Friedmann-Morvinski, Tova Waks, Assaf Marcus, and Zelig Eshhar

**Part II Evolving Clinical Immunotherapeutic Strategies

**Immunotherapy in Renal Cell Carcinoma.....Jennifer Cudris and Jaime R. Merchan

Adoptive T-Cell Transfer as a Clinical Antitumor Strategy for Hematologic Malignancies......Aaron P. Rapoport and Nadia Ijaz

Bifunctional Antibodies: Preclinical and Clinical Applications.....Casey W. Shuptrine and Louis M. Weiner

Clinical Development of Antibody-Fusion Proteins for Cancer Therapy.....Kory L. Alderson, Amy K. Erbe, Margaret Boyden, and Paul M. Sondel

Immunologic Outcomes of Allogeneic Stem Cell Transplantation: Graft-Versus-Host and Graft-Versus-Leukemia Responses and Implications for Future Therapy.....Lazaros J. Lekakis and Krishna V. Komanduri

The Immune System in Head and Neck Squamous Cell Carcinoma: Interactions and Therapeutic Opportunities.....Paolo Serafini and Donald T. Weed

T Cell Co-regulatory Signals and Their Role in Cancer Therapy......Eitan R. Friedman, Lynn Feun, Pasquale Benedetto, and Joseph D. Rosenblatt

Assessment of Immune Response in Biotherapy Trials and Clinical Endpoints.....Theresa L. Whiteside

Index