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

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230 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) 11 Hybrid Cell Vaccination for Cancer Immune Therapy Peter Walden, Gernot Stuhler and Uwe Trefzer 11.1 Introduction Cases of spontaneous regressions of tumors reported for a variety of cancers have long been interpreted as the result of tumor-specific immune reactions [1]. Burnet had forged these observations from clinical cases together with the results of pathological studies and a number of animal model experiments into the concept of immune surveillance of cancer, and thereby summed up about a century of tumor immunology [2±4]. Regression zones occasionally observed in melanoma lesions are frequently referred to as illustrations of cellular immune reactions against the tumor and correlated with a better prognosis [5, 6]. Such clinical observation together with an increasing number of reports that demonstrate greatly expanded frequencies of tumor-specific T cells in cancer patients [7±28] are indicative of active antitumor immune responses. For several tumor-associated antigens (TAAs), expanded frequencies of specific T cells have even been demonstrated in healthy individuals [29]. However, regression areas in melanoma are often seen together with simultaneous tumor progression at the border zones of the same tumor and, at later stages of the disease, increasing immune dysfunctions are described in many patients which gradually eliminate effective specific antitumor immune responses. All these observations suggest an ongoing struggle of the tumor and the immune system, with tumor progression being the result of a shift in favor of the tumor and tumor regression a shift in favor of the immune system. Vaccination for cancer immune therapy thus seems to aim at a specific modulation of the quality and quantity of this balance, and, maybe, induction of new antitumor cytotoxic cellular immune responses. Currently, vaccination in cancer is primarily a therapeutic intervention in contrast to the situation in the case of infectious diseases. Preventive vaccination against cancer is not yet possible in humans, but might be attempted in future in specific high-risk situations. Prerequisite of an active role of adaptive immune responses against cancer is a specific antigenicity of the tumor cells. The development of specific vaccination strategies for cancer immune therapy depends on TAAs, but also on the identification of the effector mechanism used by the immune system. Burnet et al. had suggested already some 30 years ago that T lymphocytes are the solely most important effector cells in
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Cancer Immune Therapie: Current and
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Editors: Dr. Gernot Stuhler Univers
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VI Preface Recent years have seen a
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VIII Contents 2.5.3 Antigens Encode
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X Contents 6.4.2 Natural Killer (NK
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XII Contents 9.6 Loading DC with An
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XIV Contents 14.2.2.1 Cancer-specif
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List of Contributors Richard Bucala
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Color Plates Fig. 5.2 The MHC class
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Fig. 5.5 Different immune effector
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Fig. 5.17 Possible pathway for the
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Fig. 6.2 T lymphocytes in the tumor
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Index a acidic and basic fibroblast
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±, see also tumors cationic lipids
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e EBV see Epstein-Barr virus EDR se
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immature Mo-DCs 184 immune cells ±
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MHC class I antigen-processing mach
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±, onco- 209 ±, over-expressed ce
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TICD see tumor-induced cell death T
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Part 1 Tumor Antigenicity Cancer Im
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4 1 Search for Universal Tumor-Asso
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10 1 Search for Universal Tumor-Ass
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18 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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Page 211 and 212: Part 3 Strategies for Cancer Immuno
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Page 239 and 240: 206 10 The Immune System in Cancer:
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Page 303 and 304: 270 13 Applications of CpG Motifs f
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280 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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