ADVANCEMENTS IN TUMOR IMMUNOTHERAPY AND CANCER VACCINES Edited by Hilal Arnouk Advancements in Tumor Immunotherapy and Cancer Vaccines Edited by Hilal Arnouk Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Petra Nenadic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published January, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Advancements in Tumor Immunotherapy and Cancer Vaccines, Edited by Hilal Arnouk p. cm. ISBN: 978-953-307-998-1 Contents Preface IX Chapter 1 Immunotherapy in Urologic Malignancies: The Evolution and Future of Pattern Recognition Receptors 1 Jane Lee and Arnold I. Chin Chapter 2 Vaccine and Cancer Therapy for Genitourinary Tumors 21 Robert J. Amato and Mika Stepankiw Chapter 3 Challenges to Prostate Cancer Immunotherapy 37 Elena N. Klyushnenkova and Richard B. Alexander Chapter 4 Prostate Cancer Immunotherapy – Strategy with a Synthetic GnRH Based Vaccine Candidate 63 J.A. Junco, F. Fuentes, R. Basulto, E. Bover, M.D. Castro, E. Pimentel, O. Reyes, R. Bringas, L.Calzada, Y. López, N. Arteaga, A. Rodríguez, H. Garay, R. Rodríguez, L. González-Quiza, L. Fong and G.E. Guillén Chapter 5 Immune-Therapy in Cutaneous Melanoma – Efficacy Immune Markers 83 Monica Neagu and Carolina Constantin Chapter 6 Innate Immunity-Based Immunotherapy of Cancer 107 Kouji Maruyama, Hidee Ishii, Sachiko Tai, Jinyan Cheng, Takatomo Satoh, Sachiko Karaki, Shingo Akimoto and Ken Yamaguchi Chapter 7 The Potential Use of Triterpene Compounds in Dendritic Cells-Based Immunotherapy 143 Masao Takei, Akemi Umeyama and Je-Jung Lee Chapter 8 The Novel Use of Zwitterionic Bacterial Components and Polysaccharides in Immunotherapy of Cancer and Immunosuppressed Cancer Patients 155 A.S. Abdulamir, R.R. Hafidh and F. Abubaker VI Contents Chapter 9 Type III Interferons IL-28 and IL-29: Novel Interferon Family Members with Therapeutic Potential in Cancer Therapy 175 Hitomi Fujie and Muneo Numasaki Chapter 10 Interleukin 12: Stumbling Blocks and Stepping Stones to Effective Anti-Tumor Therapy 197 Hollie J. Pegram, Alena A. Chekmasova, Gavin H. Imperato and Renier J. Brentjens Preface Suddenly we heard a voice crying, "This is the sea. This is the deep sea. This is the vast and mighty sea." And when we reached the voice it was a man whose back was turned to the sea, and at his ear he held a shell, listening to its murmur” Khalil Gibran – The Madman For decades we have been learning about the interplay between tumors and the immune system. Our knowledge seemed somewhat incomplete and indirect, like listening to the ocean waves through a shell. Only recently, cancer immunotherapy has started to become a reality, with Provenge (Dendreon Corporation, WA), an autologous antigen-presenting cell preparation, earning the approval of United States Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in 2010. This book provides an excellent review of the field of cancer immunotherapy, with special focus on prostate cancer, one of the most common cancers and a leading cause of cancer deaths in industrialized countries. The directions of immunotherapy of melanomas are also dicsussed in some detail within this book. Several chapters are dedicated to novel immunotherapeutic approaches utilizing the immunostimulatory functions of cell-based and protein-based vaccines, Toll-like receptors, Glycosphingolipids, Stress molecules, Type III Interferons, Interleukin 12 and biological plant-based compounds such as Triterpenes. I would like to thank the people who helped with this publication, especially Ms Petra Nenadic. Finally, I dedicate this book to my family, my mentors and mentees throughout my career. Hilal Arnouk, MD, PhD Director of Research and Development, Cell Constructs, Inc., Affiliated with Georgia State University, Atlanta, GA, USA [...]... recognizes, and eliminates developing tumors Tumor surveillance necessitates recognition of tumor antigens or “altered” self-antigens, and gained acceptance as new models emerged in the field of immunology This included pre-clinical studies 2 Advancements in Tumor Immunotherapy and Cancer Vaccines demonstrating tumor sensitivity to IFN treatment in vivo and increased carcinogen– induced tumor formation in. .. chemokines involved in autocrine and paracrine signaling cascades, and understanding its molecular mechanisms will be central in 4 Advancements in Tumor Immunotherapy and Cancer Vaccines understanding the paradigm on how inflammation influences tumorigenesis The discovery of Toll-like receptors has provided insight into a molecular basis for antigen recognition and modulation of innate and adaptive immunity,... dualistic understanding of inflammation and cancer 3 Components of the tumor microenvironment The tumor microenvironment consists of a complex milieu of stromal and inflammatory cells, soluble factors, and extracellular matrix, intertwined with tumor cells Identifying and understanding the regulation of the tumor microenvironment will be critical in designing therapies to inhibit tumor growth and invasion... network in the tumor tissue Bioconjug Chem 20 Advancements in Tumor Immunotherapy and Cancer Vaccines Zoglmeier, C., Bauer, H., Norenberg, D., Wedekind, G., Bittner, P., Sandholzer, N., Rapp, M., Anz, D., Endres, S., and Bourquin, C (2011) CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor- bearing mice Clin Cancer Res 17, 1765-1775 2 Vaccine and Cancer Therapy for Genitourinary Tumors... Evolution and Future of Pattern Recognition Receptors 5 3.3 Cytokines and chemokines Cytokines and chemokines provide autocrine and paracrine signaling and play a critical role in shaping the tumor microenvironment These include cytokines that favor development of anti -tumor immunity include IL-12, IFN, and IFN and those that enhance immune suppression such as IL-10, IL-17, and TGF or tumor progression... 2007) Supporting a role in tumorigenesis, MyD88 mediates tumor initiation in a mouse model of spontaneous intestinal tumorigenesis and diethylnitrosamine-induced hepatocellular tumors (Naugler et al., 2007; RakoffNahoum and Medzhitov, 2007; Xie et al., 2007) These opposing effects are confounded by the tumor origin, tumor model used, and potential contribution of TLRs on tumor cells, and further studies... and 4 pathways as well Recent trials utilizing components of mycobacterial cell walls rather than live bacteria may have similar efficacy while reducing toxicity (Chin et al., 1996) In fact, activation of TLRs using synthetic PAMPs reduces tumor 12 Advancements in Tumor Immunotherapy and Cancer Vaccines growth in pre-clinical models in bladder and prostate cancer With the impact of IFN in kidney cancer. .. with tumor cells by Rudolf Virchow in 1863 marked the link between inflammation and cancer Since then, inflammation has been shown to play distinct roles during tumor initiation, promotion, and metastasis While growing evidence demonstrates the ability of chronic inflammation to initiate tumors, other examples support a role of tumor immune surveillance in cancer elimination Perhaps the role of inflammation... Genitourinary Cancer Vaccines 22 Advancements in Tumor Immunotherapy and Cancer Vaccines 2 Prostate cancer As the most common noncutaneous malignancy to affect men and the second leading cause of cancer- related deaths in men in the United States, prostate cancer is expected to afflict approximately one in six men during their lifetime (Waeckerle-Men, Allmen, Fopp, et al., 2009) Prostatectomy and radiation... transcription 10 Advancements in Tumor Immunotherapy and Cancer Vaccines factors leading to production of inflammatory target genes such as cell cycle regulator genes c-myc and cyclin D1, cell survival genes bcl-xL, angiogenesis factors including VEGF, inflammatory cytokines such as IL-1, IL-6, and IL-8, type I interferons, chemokines, and T cell co-stimulatory molecules These signals are crucial elements in the . pre-clinical studies Advancements in Tumor Immunotherapy and Cancer Vaccines 2 demonstrating tumor sensitivity to IFN treatment in vivo and increased carcinogen– induced tumor formation in. paracrine signaling cascades, and understanding its molecular mechanisms will be central in Advancements in Tumor Immunotherapy and Cancer Vaccines 4 understanding the paradigm on how inflammation. ADVANCEMENTS IN TUMOR IMMUNOTHERAPY AND CANCER VACCINES Edited by Hilal Arnouk Advancements in Tumor Immunotherapy and Cancer Vaccines Edited by Hilal