Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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16.5.1 Treatment of Tumor Metastases with Immunocytokines 330 16.5.2 Tumor Targeting of LT-aInduces a Peripheral Lymphoid-like Tissue Leading to an Efficient Immune Response against Melanoma 333 16.5.3 ch14.18±IL-2 Immunocytokine Boosts Protective Immunity Induced by an Autologous Oral DNA Vaccine against Murine Melanoma 334 16.6 Neuroblastoma 337 16.6.1 Treatment with ch14.18±IL-2 Immunocytokine 337 16.6.2 Immunocytokine Treatment of Bone Marrow and Liver Metastases 337 16.6.3 Mechanism of Immunocytokine-mediated Immune Responses 338 16.6.4 Amplification of Suboptimal CD8 + T Memory Cells by a Cellular Vaccine 340 16.6.5 Synergy between Targeted IL-2 and Antiangiogensis 341 16.7 Conclusions and Perspectives 342 Acknowledgments 342 References 343 17 Immunotoxins and Recombinant Immunotoxins in Cancer Therapy 347 Yoram Reiter and Avital Lev 17.1 Introduction 347 17.2 First- and Second-Generation Immunotoxins 350 17.3 The Development of Recombinant DNA-based Immunotoxins: Design of Recombinant Immunotoxins 351 17.3.1 The Toxin Moiety 351 17.3.1.1 Plant toxins 351 17.3.1.2 Bacterial toxins: DTand DT derivatives 352 17.3.1.3 Bacterial toxins: PE and PE derivatives 353 17.3.2 The Targeting Moiety ± Recombinant Antibody Fragments 354 17.4 Construction and Production of Recombinant Immunotoxins 357 17.5 Preclinical Development of Recombinant Immunotoxins 358 17.6 Application of Recombinant Immunotoxins 360 17.6.1 Recombinant Immunotoxins against Solid Tumors 360 17.6.2 Recombinant Immunotoxins against Leukemias and Lymphomas 361 17.7 Isolation of New and Improved Antibody Fragments as Targeting Moieties: Display Technologies for the Improvement of Immunotoxin Activity 363 17.8 Improving the Therapeutic Window of Recombinant Immunotoxins: The Balance of Toxicity, Immunogenicity and Efficacy 366 17.8.1 Immune Responses and Dose-limiting Toxicity 367 17.8.2 Specificity Dictated by the Targeting Moiety 368 17.9 Conclusions and Perspectives 369 References 369 Glossary 380 Index 395 Contents XV
List of Contributors Richard Bucala Section of Rheumatology Department of Internal Medicine School of Medicine Yale University New Haven, 06520-8031 USA Fabio Ciceri and Claudio Bordignon Fondazione Centro S. Raffaele/ Monte Tabor Istituto Di Ricovero E Cuva A Carattere Scientifico Via Olgettina 60 20132 Milano Italy Prof. Zelig Eshhar Department of Chemical Immunology The Weizmann Institute of Science P.O. Box 26 Rehovot 76100 Israel Prof. Derek Hart Mater Medical Research Institute Aubigny Place Raymond Terrace South Brisbane QLD 4101 Australia Cancer Immune Therapie: Current and Future Strategies Edited by G. Stuhler and P. Walden Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5 (Electronic) Peter-M. Kloetzel and Alice Sijts Charit -Humboldt Universitåt zu Berlin Institut fçr Biochemie Monbijoustrasse 2 10117 Berlin Germany Arthur M. Krieg, MD Coley Pharmaceutical Group 93 Worcester St. Suite 101 Wellesley, MA 02481 USA Zihai Li, M.D., PhD. Center for Immunotherapy of Cancer and Infectious Diseases, MC 1601 University of Connecticut School of Medicine 263 Farmington Avenue Farmington, CT 06030-1601 USA Christine Metz, PhD Assistant Investigator NS-LIJ Research Institute 350Community Drive Manhasset, NY 11030 USA XVII
Page 1 and 2: Cancer Immune Therapie: Current and
Page 3 and 4: Editors: Dr. Gernot Stuhler Univers
Page 5 and 6: VI Preface Recent years have seen a
Page 7 and 8: VIII Contents 2.5.3 Antigens Encode
Page 9 and 10: X Contents 6.4.2 Natural Killer (NK
Page 11 and 12: XII Contents 9.6 Loading DC with An
Page 13: XIV Contents 14.2.2.1 Cancer-specif
Page 17 and 18: Color Plates Fig. 5.2 The MHC class
Page 19 and 20: Fig. 5.5 Different immune effector
Page 21 and 22: Fig. 5.17 Possible pathway for the
Page 23 and 24: Fig. 6.2 T lymphocytes in the tumor
Page 25 and 26: Index a acidic and basic fibroblast
Page 27 and 28: ±, see also tumors cationic lipids
Page 29 and 30: e EBV see Epstein-Barr virus EDR se
Page 31 and 32: immature Mo-DCs 184 immune cells ±
Page 33 and 34: MHC class I antigen-processing mach
Page 35 and 36: ±, onco- 209 ±, over-expressed ce
Page 37 and 38: TICD see tumor-induced cell death T
Page 39 and 40: Part 1 Tumor Antigenicity Cancer Im
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28 2 Serological Determinants On Tu
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30 Cancer Immune Therapie: Current
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32 3 Processing and Presentation of
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42 4 T Cells In Tumor Immunity cult
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44 4 T Cells In Tumor Immunity cell
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46 4 T Cells In Tumor Immunity to T
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48 4 T Cells In Tumor Immunity Alth
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50 4 T Cells In Tumor Immunity Tab.
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52 4 T Cells In Tumor Immunity rest
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54 4 T Cells In Tumor Immunity 53 T
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Part 2 Immune Evasion and Suppressi
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60 5 Major Histocompatibility Compl
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68 Tab. 5.1 HLA class I loss attrib
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96 6 Immune Cells in the Tumor Micr
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98 6 Immune Cells in the Tumor Micr
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100 6 Immune Cells in the Tumor Mic
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Tab. 7.1 Effects of tumor-derived m
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122 7 Immunosuppresive Factors in C
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156 8 Interleukin-10 in Cancer Immu
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Part 3 Strategies for Cancer Immuno
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180 9 Dendritic Cells and Cancer: P
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206 10 The Immune System in Cancer:
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254 12 Principles and Strategies Em
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270 13 Applications of CpG Motifs f
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288 14 The T-Body Approach: Towards
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300 15 Bone Marrow Transplantation
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312 16 Immunocytokines: Versatile M
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348 17 Immunotoxins and Recombinant
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382 Glossary tion to the variable d
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384 Glossary suppressor gene produc
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386 Glossary press the proper recep
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388 Glossary gp96 See Chaperone. Gr
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390 Glossary cytes and addressing l
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392 Glossary T bodies are being tes
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