0 2 Ex ex FW 3 7 vivo vivo FW 8 18 activation activation NN 19 21 of of IN 22 36 tumor-draining tumor-draining JJ 37 42 lymph lymph NN 43 47 node node NN 48 49 T t NN 50 55 cells cell NNS 56 64 reverses reverse VBZ 65 72 defects defect NNS 73 75 in in IN 76 82 signal signal NN 83 95 transduction transduction NN 96 105 molecules molecule NNS 105 106 . . . 108 111 The the DT 112 120 adoptive adoptive JJ 121 129 transfer transfer NN 130 132 of of IN 133 147 tumor-draining tumor-draining JJ 148 153 lymph lymph NN 154 158 node node NN 159 160 ( ( ( 160 162 LN LN NNP 162 163 ) ) ) 164 165 T t NN 166 171 cells cell NNS 172 181 activated activate VBD 182 184 ex ex FW 185 189 vivo vivo FW 190 194 with with IN 195 203 anti-CD3 anti-cd3 NN 204 207 and and CC 208 219 interleukin interleukin NN 220 221 2 2 CD 222 223 ( ( ( 223 227 IL-2 il-2 NN 227 228 ) ) ) 229 237 mediates mediate VBZ 238 241 the the DT 242 252 regression regression NN 253 255 of of IN 256 259 the the DT 260 266 poorly poorly RB 267 278 immunogenic immunogenic JJ 279 285 murine murine JJ 286 294 melanoma melanoma NN 295 297 D5 d5 NN 297 298 . . . 299 302 The the DT 303 311 efficacy efficacy NN 312 314 of of IN 315 318 the the DT 319 328 activated activate VBN 329 331 LN ln NN 332 337 cells cell NNS 338 340 is be VBZ 341 350 augmented augment VBN 351 355 when when WRB 356 359 the the DT 360 371 sensitizing sensitize VBG 372 377 tumor tumor NN 378 380 is be VBZ 381 382 a a DT 383 394 genetically genetically RB 395 403 modified modify VBN 404 411 variant variant NN 412 413 ( ( ( 413 423 designated designate VBN 424 428 D5G6 D5G6 NNP 428 429 ) ) ) 430 434 that that WDT 435 443 secretes secrete VBZ 444 485 granulocyte/macrophage-colony-stimulating granulocyte/macrophage-colony-stimulating JJ 486 492 factor factor NN 492 493 . . . 494 496 In in IN 497 505 contrast contrast NN 506 508 to to TO 509 532 anti-CD3/IL-2-activated anti-cd3/il-2-activated JJ 533 535 LN ln NN 536 541 cells cell NNS 541 542 , , , 543 551 adoptive adoptive JJ 552 560 transfer transfer NN 561 563 of of IN 564 571 freshly freshly RB 572 580 isolated isolate VBN 581 595 tumor-draining tumor-draining JJ 596 598 LN LN NNP 599 600 T t NN 601 606 cells cell NNS 607 610 has have VBZ 611 613 no no DT 614 625 therapeutic therapeutic JJ 626 634 activity activity NN 634 635 . . . 636 638 To to TO 639 648 determine determine VB 649 656 whether whether IN 657 660 the the DT 661 672 acquisition acquisition NN 673 675 of of IN 676 685 antitumor antitumor JJ 686 694 function function NN 695 701 during during IN 702 704 ex ex FW 705 709 vivo vivo FW 710 720 activation activation NN 721 723 is be VBZ 724 734 associated associate VBN 735 739 with with IN 740 753 modifications modification NNS 754 756 in in IN 757 763 signal signal NN 764 776 transduction transduction NN 777 785 capacity capacity NN 785 786 , , , 787 790 the the DT 791 798 protein protein NN 799 807 tyrosine tyrosine NN 808 815 kinases kinase NNS 816 822 p56lck p56lck NN 823 826 and and CC 827 833 p59fyn p59fyn NN 834 837 and and CC 838 846 proteins protein NNS 847 849 of of IN 850 853 the the DT 854 863 NF-kappaB NF-kappaB NNP 864 870 family family NN 871 875 were be VBD 876 884 analyzed analyze VBN 885 887 in in IN 888 902 tumor-draining tumor-draining JJ 903 905 LN LN NNP 906 907 T t NN 908 913 cells cell NNS 913 914 . . . 915 918 The the DT 919 925 levels level NNS 926 928 of of IN 929 935 p56lck p56lck NN 936 939 and and CC 940 946 p59fyn p59fyn NN 947 951 were be VBD 952 957 lower low JJR 958 960 in in IN 961 975 tumor-draining tumor-draining JJ 976 980 than than IN 981 983 in in IN 984 990 normal normal JJ 991 993 LN LN NNP 994 995 T t NN 996 1001 cells cell NNS 1002 1005 and and CC 1006 1016 production production NN 1017 1019 of of IN 1020 1043 tyrosine-phosphorylated tyrosine-phosphorylated JJ 1044 1054 substrates substrate NNS 1055 1058 was be VBD 1059 1067 markedly markedly RB 1068 1077 depressed depress VBN 1078 1087 following follow VBG 1088 1096 anti-CD3 anti-cd3 JJ 1097 1108 stimulation stimulation NN 1108 1109 . . . 1110 1115 After after IN 1116 1121 5-day 5-day JJ 1122 1135 anti-CD3/IL-2 anti-cd3/il-2 NN 1136 1146 activation activation NN 1146 1147 , , , 1148 1154 levels level NNS 1155 1157 of of IN 1158 1164 p56lck p56lck NN 1165 1168 and and CC 1169 1175 p59fyn p59fyn NN 1176 1179 and and CC 1180 1187 protein protein NN 1188 1196 tyrosine tyrosine NN 1197 1203 kinase kinase NNP 1204 1212 activity activity NN 1213 1222 increased increase VBD 1222 1223 . . . 1224 1237 Interestingly interestingly RB 1237 1238 , , , 1239 1242 the the DT 1243 1249 levels level NNS 1250 1252 of of IN 1253 1259 p56lck p56lck NN 1259 1260 , , , 1261 1267 p59fyn p59fyn NN 1267 1268 , , , 1269 1272 and and CC 1273 1281 tyrosine tyrosine NN 1282 1288 kinase kinase NNP 1289 1297 activity activity NN 1298 1302 were be VBD 1303 1309 higher high JJR 1310 1312 in in IN 1313 1322 activated activate VBN 1323 1324 T t NN 1325 1330 cells cell NNS 1331 1338 derived derive VBN 1339 1343 from from IN 1344 1346 LN LN NNP 1347 1351 that that WDT 1352 1359 drained drain VBD 1360 1364 D5G6 d5g6 NN 1365 1369 than than IN 1370 1374 they they PRP 1375 1379 were be VBD 1380 1382 in in IN 1383 1388 those those DT 1389 1393 from from IN 1394 1396 D5 D5 NNP 1397 1403 tumors tumor NNS 1403 1404 . . . 1405 1407 In in IN 1408 1416 contrast contrast NN 1416 1417 , , , 1418 1421 the the DT 1422 1433 cytoplasmic cytoplasmic JJ 1434 1440 levels level NNS 1441 1443 of of IN 1444 1449 c-Rel c-rel NN 1450 1453 and and CC 1454 1457 Rel Rel NNP 1458 1459 A a NN 1460 1464 were be VBD 1465 1471 normal normal JJ 1472 1474 in in IN 1475 1482 freshly freshly RB 1483 1491 isolated isolate VBN 1492 1506 tumor-draining tumor-draining JJ 1507 1509 LN ln NN 1509 1510 , , , 1511 1513 as as IN 1514 1517 was be VBD 1518 1525 nuclear nuclear JJ 1526 1532 kappaB kappab NN 1533 1544 DNA-binding dna-binding JJ 1545 1553 activity activity NN 1554 1561 induced induce VBN 1562 1564 by by IN 1565 1573 anti-CD3 anti-cd3 JJ 1574 1577 mAb mab NN 1578 1580 or or CC 1581 1588 phorbol phorbol NN 1589 1598 myristate myristate NN 1599 1606 acetate acetate NN 1606 1607 . . . 1608 1619 Stimulation stimulation NN 1620 1622 of of IN 1623 1632 activated activate VBN 1633 1635 LN ln NN 1636 1641 cells cell NNS 1642 1646 with with IN 1647 1649 D5 D5 NNP 1650 1655 tumor tumor NN 1656 1661 cells cell NNS 1662 1669 induced induce VBD 1670 1673 the the DT 1674 1681 nuclear nuclear JJ 1682 1695 translocation translocation NN 1696 1698 of of IN 1699 1708 NF-kappaB NF-kappaB NNP 1708 1709 . . . 1710 1715 These these DT 1716 1724 findings finding NNS 1725 1733 indicate indicate VBP 1734 1738 that that IN 1739 1742 the the DT 1743 1751 recovery recovery NN 1752 1754 of of IN 1755 1763 proteins protein NNS 1764 1773 mediating mediate VBG 1774 1780 signal signal NN 1781 1793 transduction transduction NN 1794 1801 through through IN 1802 1805 the the DT 1806 1807 T t NN 1808 1812 cell cell NN 1813 1825 receptor/CD3 receptor/cd3 NN 1826 1833 complex complex NN 1834 1836 in in IN 1837 1839 LN LN NNP 1840 1841 T t NN 1842 1847 cells cell NNS 1848 1857 activated activate VBD 1858 1860 ex ex FW 1861 1865 vivo vivo FW 1866 1869 was be VBD 1870 1880 associated associate VBN 1881 1885 with with IN 1886 1889 the the DT 1890 1901 acquisition acquisition NN 1902 1904 of of IN 1905 1914 antitumor antitumor JJ 1915 1923 function function NN 1923 1924 . . .