35 Heiser, A., Maurice, M. A.,Yancey, D. R., Coleman, D. M., Dahm, P. <strong>and</strong> Vieweg, J. Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed <strong>by</strong> primary <strong>and</strong> metastatic tumors, <strong>Cancer</strong> Res 61: 3388±93, 2001. 36 Vonderheide, R., Anderson, K., Hahn,W., Butler, M., Schultze, J. <strong>and</strong> Nadler, L. Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase, Clin <strong>Cancer</strong> Res 61: 8366±8370, 2001. 37 Arai, J.,Yasukawa, M., Ohminami, H., Kakimoto, M., Hasegawa, A. <strong>and</strong> Fujita, S. Identification of human telomerase reverse transcriptasederived peptides that induce HLA-A24restricted antileukemia cytotoxic T lymphocytes, Blood 97: 2903±7, 2001. 38 Hahn,W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W. <strong>and</strong> Weinberg, R. A. Creation of human tumour cells with defined genetic elements, Nature 400: 464±8, 1999. 39 Greenberg, R. A., Chin, L., Femino, A., Lee, K. H., Gottlieb, G. J., Singer, R. H., Greider, C. W. <strong>and</strong> DePinho, R. A. Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse, Cell 97: 515±25, 1999. 40 Hahn,W. C., Stewart, S. A., Brooks, M. W.,York, S. G., Eaton, E., Kurachi, A., Beijersbergen, R. L., Knoll, J. H., Meyerson, M. <strong>and</strong> Weinberg, R. A. Inhibition of telomerase limits the growth of human cancer cells, Nat Med 5: 1164±70, 1999. 41 Herbert, B., Pitts, A. E., Baker, S. I., Hamilton, S. E.,Wright,W. E., Shay, J. W. <strong>and</strong> Corey, D. R. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening <strong>and</strong> cell death, Proc Natl Acad Sci USA. 96: 14276±81, 1999. 42 Jager, E., Ringhoffer, M., Karbach, J., Ar<strong>and</strong>, M., Oesch, F. <strong>and</strong> Knuth, A. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues <strong>and</strong> CD8 + cytotoxic-T-cell References responses: evidence for immunoselection of antigen-loss variants in vivo, Int J <strong>Cancer</strong> 66: 470±6, 1996. 43 Harle-Bachor, C. <strong>and</strong> Boukamp, P. Telomerase activity in the regenerative basal layer of the epidermis inhuman skin <strong>and</strong> in immortal <strong>and</strong> carcinomaderived skin keratinocytes, Proc Natl Acad Sci USA 93: 6476±81, 1996. 44 Yasumoto, S., Kunimura, C., Kikuchi, K., Tahara, H., Ohji, H., Yamamoto, H., Ide, T. <strong>and</strong> Utakoji, T. Telomerase activity in normal human epithelial cells, Oncogene 13: 433±9, 1996. 45 Norrback, K. F. <strong>and</strong> Roos, G. Telomeres <strong>and</strong> telomerase in normal <strong>and</strong> malignant haematopoietic cells, Eur J <strong>Cancer</strong> 33: 774±80, 1997. 46 Baltimore, D. Our genome unveiled, Nature 409: 814±6, 2001. 47 Schmitz, M., Diestelkoetter, P., Weigle, B., Schmachtenberg, F., Stevanovic, S., Ockert, D., Rammensee, H. G. <strong>and</strong> Rieber, E. P. Generation of survivin-specific CD8 + Teffector cells <strong>by</strong> dendritic cells pulsed with protein or selected peptides, <strong>Cancer</strong> Res 60: 4845± 9, 2000. 48 van der Bruggen, P., Bastin, J., Gajewski, T., Coulie, P. G., Boel, P., De Smet, C., Traversari, C., Townsend, A. <strong>and</strong> Boon, T. A peptide encoded <strong>by</strong> human gene MAGE-3 <strong>and</strong> presented <strong>by</strong> HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3, Eur JImmunol 24: 3038± 43, 1994. 49 Melief, C. J. <strong>and</strong> Kast,W. M. T-cell immunotherapy of cancer, Res Immunol 142: 425±9, 1991. 50 Gedde-Dahl, T., III, Fossum, B., Eriksen, J. A., Thors<strong>by</strong>, E. <strong>and</strong> Gaudernack, G. T cell clones specific for p21 ras -derived peptides: characterization of their fine specificity <strong>and</strong> HLA restriction, Eur JImmunol 23: 754±60, 1993. 51 Chen,W., Peace, D. J., Rovira, D. K., You, S. G. <strong>and</strong> Cheever, M. A. T-cell immunity to the joining region of p210 BCR±ABL protein, Proc Natl Acad Sci USA 89: 1468±72, 1992. 15
16 1 Search for Universal Tumor-Associated T Cell Epitopes 52 Molldrem, J., Dermime, S., Parker, K., Jiang,Y. Z., Mavroudis, D., Hensel, N., Fukushima, P. <strong>and</strong> Barrett, A. J. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells, Blood 88: 2450±7, 1996. 53 Gaiger, A., Reese,V., Disis, M. L. <strong>and</strong> Cheever, M. A. Immunity to WT1 in the animal model <strong>and</strong> in patients with acute myeloid leukemia, Blood 96: 1480± 9, 2000. 54 Tsang, K. Y., Zaremba, S., Nieroda, C. A., Zhu, M. Z., Hamilton, J. M. <strong>and</strong> Schlom, J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine, JNatl <strong>Cancer</strong> Inst 87: 982±90, 1995. 55 Correale, P.,Walmsley, K., Zaremba, S., Zhu, M., Schlom, J. <strong>and</strong> Tsang, K. Y. Generation of human cytolytic T lymphocyte lines directed against prostate-specific antigen (PSA) employing a PSA oligoepitope peptide, JImmunol 161: 3186± 94, 1998. 56 Ioannides, C. G., Fisk, B., Jerome, K. R., Irimura, T.,Wharton, J. T. <strong>and</strong> Finn, O. J. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides, JImmunol 151: 3693±703, 1993. 57 Brossart, P., Heinrich, K. S., <strong>Stuhler</strong>, G., Behnke, L., Reichardt,V. L., Stevanovic, S., Muhm, A., Rammensee, H. G., Kanz, L. <strong>and</strong> Brugger,W. Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies, Blood 93: 4309±17, 1999. 58 Peoples, G. E., Anderson, B. W., Lee, T. V., Murray, J. L., Kudelka, A. P., Wharton, J. T. <strong>and</strong> Ioannides, C. G. Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyterecognized antigen system in epithelial cancers, Clin <strong>Cancer</strong> Res 5: 4214±23, 1999. 59 Trojan, A.,Witzens, M., Schultze, J. L., Vonderheide, R. H., Harig, S., Krackhardt, A. M., Stahel, R. A. <strong>and</strong> Gribben, J. G. Generation of cytotoxic T lymphocytes against native <strong>and</strong> altered peptides of human leukocyte antigen- A*0201 restricted epitopes from the human epithelial cell adhesion molecule, <strong>Cancer</strong> Res 61: 4761±5, 2001.
- 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 and 14: XIV Contents 14.2.2.1 Cancer-specif
- Page 15 and 16: List of Contributors Richard Bucala
- 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
- Page 41 and 42: 4 1 Search for Universal Tumor-Asso
- Page 43 and 44: 6 1 Search for Universal Tumor-Asso
- Page 45 and 46: 8 1 Search for Universal Tumor-Asso
- Page 47 and 48: 10 1 Search for Universal Tumor-Ass
- Page 49 and 50: 12 1 Search for Universal Tumor-Ass
- Page 51: 14 1 Search for Universal Tumor-Ass
- Page 55 and 56: 18 2 Serological Determinants On Tu
- Page 57 and 58: 20 2 Serological Determinants On Tu
- Page 59 and 60: 22 2 Serological Determinants On Tu
- Page 61 and 62: 24 2 Serological Determinants On Tu
- Page 63 and 64: 26 2 Serological Determinants On Tu
- Page 65 and 66: 28 2 Serological Determinants On Tu
- Page 67 and 68: 30 Cancer Immune Therapie: Current
- Page 69 and 70: 32 3 Processing and Presentation of
- Page 71 and 72: 34 3 Processing and Presentation of
- Page 73 and 74: 36 3 Processing and Presentation of
- Page 75 and 76: 38 3 Processing and Presentation of
- Page 77 and 78: 40 Cancer Immune Therapie: Current
- Page 79 and 80: 42 4 T Cells In Tumor Immunity cult
- Page 81 and 82: 44 4 T Cells In Tumor Immunity cell
- Page 83 and 84: 46 4 T Cells In Tumor Immunity to T
- Page 85 and 86: 48 4 T Cells In Tumor Immunity Alth
- Page 87 and 88: 50 4 T Cells In Tumor Immunity Tab.
- Page 89 and 90: 52 4 T Cells In Tumor Immunity rest
- Page 91 and 92: 54 4 T Cells In Tumor Immunity 53 T
- Page 93 and 94: Part 2 Immune Evasion and Suppressi
- Page 95 and 96: 60 5 Major Histocompatibility Compl
- Page 97 and 98: 62 5 Major Histocompatibility Compl
- Page 99 and 100: 64 5 Major Histocompatibility Compl
- Page 101 and 102: 66 5 Major Histocompatibility Compl
- Page 103 and 104:
68 Tab. 5.1 HLA class I loss attrib
- Page 105 and 106:
70 5 Major Histocompatibility Compl
- Page 107 and 108:
72 5 Major Histocompatibility Compl
- Page 109 and 110:
74 5 Major Histocompatibility Compl
- Page 111 and 112:
76 5 Major Histocompatibility Compl
- Page 113 and 114:
78 5 Major Histocompatibility Compl
- Page 115 and 116:
80 5 Major Histocompatibility Compl
- Page 117 and 118:
82 5 Major Histocompatibility Compl
- Page 119 and 120:
84 5 Major Histocompatibility Compl
- Page 121 and 122:
86 5 Major Histocompatibility Compl
- Page 123 and 124:
88 5 Major Histocompatibility Compl
- Page 125 and 126:
90 5 Major Histocompatibility Compl
- Page 127 and 128:
92 5 Major Histocompatibility Compl
- Page 129 and 130:
94 5 Major Histocompatibility Compl
- Page 131 and 132:
96 6 Immune Cells in the Tumor Micr
- Page 133 and 134:
98 6 Immune Cells in the Tumor Micr
- Page 135 and 136:
100 6 Immune Cells in the Tumor Mic
- Page 137 and 138:
102 6 Immune Cells in the Tumor Mic
- Page 139 and 140:
104 6 Immune Cells in the Tumor Mic
- Page 141 and 142:
106 6 Immune Cells in the Tumor Mic
- Page 143 and 144:
108 6 Immune Cells in the Tumor Mic
- Page 145 and 146:
110 6 Immune Cells in the Tumor Mic
- Page 147 and 148:
112 6 Immune Cells in the Tumor Mic
- Page 149 and 150:
114 6 Immune Cells in the Tumor Mic
- Page 151 and 152:
116 6 Immune Cells in the Tumor Mic
- Page 153 and 154:
118 6 Immune Cells in the Tumor Mic
- Page 155 and 156:
Tab. 7.1 Effects of tumor-derived m
- Page 157 and 158:
122 7 Immunosuppresive Factors in C
- Page 159 and 160:
124 7 Immunosuppresive Factors in C
- Page 161 and 162:
126 7 Immunosuppresive Factors in C
- Page 163 and 164:
128 7 Immunosuppresive Factors in C
- Page 165 and 166:
130 7 Immunosuppresive Factors in C
- Page 167 and 168:
132 7 Immunosuppresive Factors in C
- Page 169 and 170:
134 7 Immunosuppresive Factors in C
- Page 171 and 172:
136 7 Immunosuppresive Factors in C
- Page 173 and 174:
138 7 Immunosuppresive Factors in C
- Page 175 and 176:
140 7 Immunosuppresive Factors in C
- Page 177 and 178:
142 7 Immunosuppresive Factors in C
- Page 179 and 180:
144 7 Immunosuppresive Factors in C
- Page 181 and 182:
146 7 Immunosuppresive Factors in C
- Page 183 and 184:
148 7 Immunosuppresive Factors in C
- Page 185 and 186:
150 7 Immunosuppresive Factors in C
- Page 187 and 188:
152 7 Immunosuppresive Factors in C
- Page 189 and 190:
154 7 Immunosuppresive Factors in C
- Page 191 and 192:
156 8 Interleukin-10 in Cancer Immu
- Page 193 and 194:
158 8 Interleukin-10 in Cancer Immu
- Page 195 and 196:
160 8 Interleukin-10 in Cancer Immu
- Page 197 and 198:
162 8 Interleukin-10 in Cancer Immu
- Page 199 and 200:
164 8 Interleukin-10 in Cancer Immu
- Page 201 and 202:
166 8 Interleukin-10 in Cancer Immu
- Page 203 and 204:
168 8 Interleukin-10 in Cancer Immu
- Page 205 and 206:
170 8 Interleukin-10 in Cancer Immu
- Page 207 and 208:
172 8 Interleukin-10 in Cancer Immu
- Page 209 and 210:
174 8 Interleukin-10 in Cancer Immu
- Page 211 and 212:
Part 3 Strategies for Cancer Immuno
- Page 213 and 214:
180 9 Dendritic Cells and Cancer: P
- Page 215 and 216:
182 9 Dendritic Cells and Cancer: P
- Page 217 and 218:
184 9 Dendritic Cells and Cancer: P
- Page 219 and 220:
186 9 Dendritic Cells and Cancer: P
- Page 221 and 222:
188 9 Dendritic Cells and Cancer: P
- Page 223 and 224:
190 9 Dendritic Cells and Cancer: P
- Page 225 and 226:
192 9 Dendritic Cells and Cancer: P
- Page 227 and 228:
194 9 Dendritic Cells and Cancer: P
- Page 229 and 230:
196 9 Dendritic Cells and Cancer: P
- Page 231 and 232:
198 9 Dendritic Cells and Cancer: P
- Page 233 and 234:
200 9 Dendritic Cells and Cancer: P
- Page 235 and 236:
202 9 Dendritic Cells and Cancer: P
- Page 237 and 238:
204 Cancer Immune Therapie: Current
- Page 239 and 240:
206 10 The Immune System in Cancer:
- Page 241 and 242:
208 10 The Immune System in Cancer:
- Page 243 and 244:
210 10 The Immune System in Cancer:
- Page 245 and 246:
212 10 The Immune System in Cancer:
- Page 247 and 248:
214 10 The Immune System in Cancer:
- Page 249 and 250:
216 10 The Immune System in Cancer:
- Page 251 and 252:
218 10 The Immune System in Cancer:
- Page 253 and 254:
220 10 The Immune System in Cancer:
- Page 255 and 256:
222 10 The Immune System in Cancer:
- Page 257 and 258:
224 10 The Immune System in Cancer:
- Page 259 and 260:
226 10 The Immune System in Cancer:
- Page 261 and 262:
228 10 The Immune System in Cancer:
- Page 263 and 264:
230 Cancer Immune Therapie: Current
- Page 265 and 266:
232 11 Hybrid Cell Vaccination for
- Page 267 and 268:
234 11 Hybrid Cell Vaccination for
- Page 269 and 270:
236 11 Hybrid Cell Vaccination for
- Page 271 and 272:
238 11 Hybrid Cell Vaccination for
- Page 273 and 274:
240 11 Hybrid Cell Vaccination for
- Page 275 and 276:
242 11 Hybrid Cell Vaccination for
- Page 277 and 278:
244 11 Hybrid Cell Vaccination for
- Page 279 and 280:
246 11 Hybrid Cell Vaccination for
- Page 281 and 282:
248 11 Hybrid Cell Vaccination for
- Page 283 and 284:
250 11 Hybrid Cell Vaccination for
- Page 285 and 286:
252 11 Hybrid Cell Vaccination for
- Page 287 and 288:
254 12 Principles and Strategies Em
- Page 289 and 290:
256 12 Principles and Strategies Em
- Page 291 and 292:
258 12 Principles and Strategies Em
- Page 293 and 294:
260 12 Principles and Strategies Em
- Page 295 and 296:
262 12 Principles and Strategies Em
- Page 297 and 298:
264 12 Principles and Strategies Em
- Page 299 and 300:
266 12 Principles and Strategies Em
- Page 301 and 302:
268 Cancer Immune Therapie: Current
- Page 303 and 304:
270 13 Applications of CpG Motifs f
- Page 305 and 306:
272 13 Applications of CpG Motifs f
- Page 307 and 308:
274 13 Applications of CpG Motifs f
- Page 309 and 310:
276 13 Applications of CpG Motifs f
- Page 311 and 312:
278 13 Applications of CpG Motifs f
- Page 313 and 314:
280 13 Applications of CpG Motifs f
- Page 315 and 316:
282 13 Applications of CpG Motifs f
- Page 317 and 318:
284 13 Applications of CpG Motifs f
- Page 319 and 320:
286 13 Applications of CpG Motifs f
- Page 321 and 322:
288 14 The T-Body Approach: Towards
- Page 323 and 324:
290 14 The T-Body Approach: Towards
- Page 325 and 326:
292 14 The T-Body Approach: Towards
- Page 327 and 328:
294 14 The T-Body Approach: Towards
- Page 329 and 330:
296 14 The T-Body Approach: Towards
- Page 331 and 332:
298 14 The T-Body Approach: Towards
- Page 333 and 334:
300 15 Bone Marrow Transplantation
- Page 335 and 336:
302 15 Bone Marrow Transplantation
- Page 337 and 338:
304 15 Bone Marrow Transplantation
- Page 339 and 340:
306 15 Bone Marrow Transplantation
- Page 341 and 342:
308 15 Bone Marrow Transplantation
- Page 343 and 344:
310 15 Bone Marrow Transplantation
- Page 345 and 346:
312 16 Immunocytokines: Versatile M
- Page 347 and 348:
314 16 Immunocytokines: Versatile M
- Page 349 and 350:
316 16 Immunocytokines: Versatile M
- Page 351 and 352:
318 16 Immunocytokines: Versatile M
- Page 353 and 354:
320 16 Immunocytokines: Versatile M
- Page 355 and 356:
322 16 Immunocytokines: Versatile M
- Page 357 and 358:
324 16 Immunocytokines: Versatile M
- Page 359 and 360:
326 16 Immunocytokines: Versatile M
- Page 361 and 362:
328 16 Immunocytokines: Versatile M
- Page 363 and 364:
330 16 Immunocytokines: Versatile M
- Page 365 and 366:
332 16 Immunocytokines: Versatile M
- Page 367 and 368:
334 16 Immunocytokines: Versatile M
- Page 369 and 370:
336 16 Immunocytokines: Versatile M
- Page 371 and 372:
338 16 Immunocytokines: Versatile M
- Page 373 and 374:
340 16 Immunocytokines: Versatile M
- Page 375 and 376:
342 16 Immunocytokines: Versatile M
- Page 377 and 378:
344 16 Immunocytokines: Versatile M
- Page 379 and 380:
346 16 Immunocytokines: Versatile M
- Page 381 and 382:
348 17 Immunotoxins and Recombinant
- Page 383 and 384:
350 17 Immunotoxins and Recombinant
- Page 385 and 386:
352 17 Immunotoxins and Recombinant
- Page 387 and 388:
354 17 Immunotoxins and Recombinant
- Page 389 and 390:
356 17 Immunotoxins and Recombinant
- Page 391 and 392:
358 17 Immunotoxins and Recombinant
- Page 393 and 394:
360 17 Immunotoxins and Recombinant
- Page 395 and 396:
362 17 Immunotoxins and Recombinant
- Page 397 and 398:
364 17 Immunotoxins and Recombinant
- Page 399 and 400:
366 17 Immunotoxins and Recombinant
- Page 401 and 402:
368 17 Immunotoxins and Recombinant
- Page 403 and 404:
370 17 Immunotoxins and Recombinant
- Page 405 and 406:
372 17 Immunotoxins and Recombinant
- Page 407 and 408:
374 17 Immunotoxins and Recombinant
- Page 409 and 410:
376 17 Immunotoxins and Recombinant
- Page 411 and 412:
378 17 Immunotoxins and Recombinant
- Page 413 and 414:
380 Cancer Immune Therapie: Current
- Page 415 and 416:
382 Glossary tion to the variable d
- Page 417 and 418:
384 Glossary suppressor gene produc
- Page 419 and 420:
386 Glossary press the proper recep
- Page 421 and 422:
388 Glossary gp96 See Chaperone. Gr
- Page 423 and 424:
390 Glossary cytes and addressing l
- Page 425 and 426:
392 Glossary T bodies are being tes