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

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
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