142:. Later on, using T-cell epitope cloning technology, other tumor antigens with same properties were identified, including MAGE-A2, MAGE-A3, BAGE and GAGE-1. With the new approach, serological analysis of cDNA expression libraries (SEREX), several novel similar antigens were discovered, including SSX-2, NY-ESO-1, etc. Beyond these immunological methods, some gene expression techniques, including mRNA pools comparison, differential display, cDNA oligonucleotide array analysis and bioinformatic analysis, identified a multitude of tumor genes with a cancer/testis restricted expression profile. As the growing of this family, this type of tumor antigens, the genes of which expressing limitedly in malignancies of various histotypes, but not in normal tissue except testis and placenta, was named cancer testis antigen (CT antigens) by Old (1997) and Chen (1998). So far, at least 70 families of CT antigens with over 140 members have been identified and listed in a database established by the Ludwing Institute for Cancer Research.
84:. Because of their tumor-restricted expression and strong in vivo immunogenicity, CT antigens are identified as ideal targets for tumor specific immunotherapeutic approaches and prompted the development of several clinical trials of CT antigens-based vaccine therapy. CT antigens have been found to have at least 70 families so far, including about 140 members, most of which are expressed during spermatogenesis. Their expression are mainly regulated by epigenetic events, specifically, DNA methylation.
371:
The implication of CTA peptides as vaccinating agents relies on the characterization of immunogenic peptides from selected CTA and the identification of the respective HLA class I antigen restriction. To date, MAGE-A3-derived peptides have been used as vaccines in HLA-A1-positive patients with tumor
305:
during the spermatogenesis and be involved in the inhibition of cellular differentiation in cancer cells, contributing to tumorigenesis. MAGE-A11 was found to be involved in the regulation of androgen-receptor function by modulating its internal domain interactions. More studies support that the
150:
CT antigens can be divided by whether they are encoded on the X chromosome (X-CT antigens genes) or not (non-X-CT antigens genes). It has been estimated that 10% of genes on the X chromosome belong to X-CT antigens families. The X-CT antigens genes represent more than half of all CT antigens and
388:
Given some drawbacks and limitation of the inter- and intratumoral heterogeneous expression of CT antigens from the CT antigens-based vaccination, the promoter methylation in regulating CT antigens expression can be combined into the therapy to therapeutically modulate CT antigens expression in
402:
come out. In this case, the tumor-reactive T cells can be engineered to express recombinant or chimeric T-cell receptors against common tumor antigens where CT antigens could be a high priority target. Their frequent expression in many types of cancer makes CT antigen-directed T-cell therapy
278:(HDAC) works oppositely. The inhibition of HDAC by specific inhibitors (HDACi) is found to associate with the CT antigens expression in human malignancies. In addition, histone methylation is also involved in the gene expression of CT antigens, with activation and repression.
249:
and the different promoter methylation status is directly responsible for the highly heterogeneous intratumor expression of CT antigens in different cancers. This promoter methylation heterogeneity was found to be inherited by daughter cells.
397:
Infiltrating T cells therapy have been shown to apparently induce tumor regression with durable complete responses in melanoma. Expending from this approach to other types of cancers, the difficulties of obtaining tumor-infiltrating
151:
often constitute multigene families organized in well-defined clusters long the X chromosome, while the genes of non-X-CT antigens are distributed throughout the genome and are mostly single-copy genes.
575:
van der
Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. (December 1991). "A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma".
162:. In normal placenta, CT antigens genes are less common, and MAGE-A3, MAGE-8, MAGE-A10, XAGE-2 and XAGE-3 have been found there. The mRNA of CT antigens was also found in some somatic tissues such as
317:
Multiple CT antigens have been shown to promote cancer cell growth, like SSX2 in melanoma, and might also be functional in treatment responses to cytotoxic or growth inhibitory anti-cancer drugs.
356:
interacting with CT antigens proteins and recognizing it as invading structures. Thus, CT antigens can be regarded as essentially tumor-specific targets when they are expressed in cancers.
327:-specific CT antigens might be involved in this process, such as SPO11, SCP1 and HORMAD1. Moreover, some CT antigens combined with other proteins have been shown to support productive
286:
Germ cells share some features with cancers. The motile and penetrating features and colonization of primitive germ cells resemble the migration of cancer cells from primary tumor to
126:
With the development of tumor-associated antigens (TAA), the first clone of a human tumor antigen, melanoma antigen-1 (MAGE-1) was reported in 1990s, which elicited an autologous
310:
drugs. Besides, GAGE-7 was reported to have antiapoptotic properties. Some SSX family members was found to induce altered gene expression patterns, resulting in the malignant
45:
in the adult animal. However, in cancer these developmental antigens are often re-expressed and can serve as a locus of immune activation. Thus, they are often classified as
294:, germ cells exhibit characteristics similar to cancer cells. These phenomena led to the hypothesis that the activation of CT antigens in normal stomatic tissues related to
380:(DC). Besides peptide vaccines, recombinant full-length MAGE-A3 and NY-ESO-1 proteins are currently being evaluated as anti-cancer vaccines in a series of clinical trials.
298:. Although the function of CT antigens is far from understanding, increasing studies have found more evidences for some of the properties of CT antigens in recent years.
91:(LICR) maintains the "CTDatabase." This database is an authoritative list of known CT antigens. It also serves as a repository into which new candidates can be entered.
134:
patient. Further studies found that MAGE-1 (renamed MAGE-A1 later) was expressed in various cancers of different histological origin but not in normal tissues excluding
363:
presented to the immune system in association with various HLA class I or HLA class II allospecificities, eliciting both CTL and humoral immune responses.
320:
CT antigens are frequently expressed in malignant tumors, especially in metastases, when compared with the rare expression in benign neoplastic lesions.
49:. The expression of CT antigens in various malignancies is heterogeneous and often correlates with tumor progression. CT antigens have been described in
241:
catalyzed by DNA methyltransferases (DNMTs). It is found so far that the non-expression in normal somatic tissues of CT antigens genes is caused by the
422:
Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (October 2002). "Cancer/testis antigens: an expanding family of targets for cancer immunotherapy".
344:
In normal tissues, CT antigens are exclusively expressed in testis, making it no access to the immune system. Besides, the existence of
73:
offers an important role for many of these antigens in the differentiation, migration, and cell division of primordial germ cells,
185:(IHC) analysis in protein level. In tumor tissues, CT antigens are distributed widely but heterogeneously, expressing largely in
158:
that are proliferate germ cells, while non-X-CT antigens are expressed in later stages of germ-cell differentiation, such as on
17:
221:
The expression of CT antigens genes are exclusively regulated by epigenetic events both in normal and cancer tissues, while
88:
465:
Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (August 2005). "Cancer/testis antigens, gametogenesis and cancer".
258:
Histone are fundamentally componential proteins in chromosomes containing flexible N-terminal tails protruding from the
934:
306:
expression of MAGE genes in cancer cells might contribute to the malignant phenotype and the resistance to
237:
DNA methylation is commonly found to lead to silencing of gene expression with the covalent addition of a
213:. Some reports suggest that multiple CT antigens tend to be co-expressed in the same neoplastic lesion.
267:
620:"A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening"
323:
The activation of meiotic programs in cancer cells may contribute to the genome instability, and the
726:
Almeida LG, Sakabe NJ, deOliveira AR, Silva MC, Mundstein AS, Cohen T, et al. (January 2009).
302:
210:
111:
349:
779:"The biology of cancer testis antigens: putative function, regulation and therapeutic potential"
510:"The biology of cancer testis antigens: putative function, regulation and therapeutic potential"
127:
229:
post-translational modification remain the most widely characterized epigenetic factors here.
728:"CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens"
631:
584:
345:
275:
182:
38:
8:
246:
635:
588:
901:
876:
852:
827:
803:
778:
777:
Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R, et al. (April 2011).
754:
727:
703:
678:
534:
509:
508:
Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R, et al. (April 2011).
490:
447:
27:
Group of proteins united by their importance in development and in cancer immunotherapy
939:
906:
857:
808:
759:
708:
659:
654:
619:
600:
539:
482:
439:
435:
618:
Chen YT, Scanlan MJ, Sahin U, TĂĽreci O, Gure AO, Tsang S, et al. (March 1997).
451:
896:
888:
847:
839:
798:
790:
749:
739:
698:
690:
649:
639:
592:
529:
521:
494:
474:
431:
307:
794:
525:
377:
291:
222:
929:
624:
Proceedings of the
National Academy of Sciences of the United States of America
62:
923:
892:
843:
353:
295:
206:
159:
155:
77:
74:
70:
66:
46:
596:
910:
861:
812:
763:
694:
644:
543:
486:
443:
238:
54:
712:
663:
604:
372:
expressing the respective antigen. MAGE-A peptides have also been used in
744:
259:
242:
58:
399:
287:
81:
42:
877:"Oncogenic cancer/testis antigens: prime candidates for immunotherapy"
828:"Oncogenic cancer/testis antigens: prime candidates for immunotherapy"
574:
311:
154:
In normal testis, X-CT antigens genes are expressed primarily on the
478:
557:
198:
186:
163:
139:
131:
103:
50:
34:
352:(HLA) class I expression on the surface of germ cells prevent the
373:
360:
328:
324:
226:
190:
99:
95:
41:. In general, expression of these proteins is restricted to male
262:, providing targets for different modifications. The N-terminal
271:
263:
202:
194:
178:
171:
135:
301:
MAGE-A1 might repression the expression of genes required for
464:
167:
107:
725:
177:
The expression of CT antigens genes were measured mainly by
174:, but the level is normally less than 1% of that in testis.
115:
874:
825:
421:
776:
617:
507:
383:
359:
Distinct CT antigens encode for different antigenic
875:Gjerstorff MF, Andersen MH, Ditzel HJ (June 2015).
826:Gjerstorff MF, Andersen MH, Ditzel HJ (June 2015).
37:united by their importance in development and in
921:
94:Important CT antigens in cancer therapy include
193:and non-small cell lung cancers, moderately in
376:consisting of peptide-loaded monocyte-derived
392:
900:
851:
802:
753:
743:
702:
653:
643:
533:
334:
676:
253:
14:
922:
683:The Journal of Experimental Medicine
679:"New paths in human cancer serology"
403:applicable to many types of cancer.
89:Ludwig Institute for Cancer Research
24:
366:
232:
25:
951:
384:Combination with epigenetic drugs
339:
436:10.1034/j.1600-065X.2002.18803.x
868:
819:
65:, and pediatric tumors such as
770:
719:
677:Old LJ, Chen YT (April 1998).
670:
611:
568:
550:
501:
458:
415:
266:residues are often acetylated
181:in transcription level and by
13:
1:
409:
795:10.1016/j.molonc.2011.02.001
526:10.1016/j.molonc.2011.02.001
216:
7:
281:
145:
31:Cancer/testis (CT) antigens
10:
956:
738:(Database issue): D816-9.
268:histone acetyltransferases
121:
893:10.18632/oncotarget.4694
844:10.18632/oncotarget.4694
211:hematologic malignancies
597:10.1126/science.1840703
393:Adoptive T-cell therapy
350:human leukocyte antigen
732:Nucleic Acids Research
695:10.1084/jem.187.8.1163
645:10.1073/pnas.94.5.1914
467:Nature Reviews. Cancer
128:cytotoxic T-lymphocyte
424:Immunological Reviews
335:Therapeutic potential
18:Cancer-testis antigen
935:Cancer immunotherapy
346:blood-testis barrier
276:histone deacetylases
254:Histone modification
183:immunohistochemistry
130:(CTL) response in a
39:cancer immunotherapy
636:1997PNAS...94.1914C
589:1991Sci...254.1643V
201:cancers, poorly in
783:Molecular Oncology
745:10.1093/nar/gkn673
514:Molecular Oncology
389:neoplastic cells.
331:in cancer cells.
16:(Redirected from
947:
915:
914:
904:
887:(18): 15772–87.
872:
866:
865:
855:
838:(18): 15772–87.
823:
817:
816:
806:
774:
768:
767:
757:
747:
723:
717:
716:
706:
674:
668:
667:
657:
647:
615:
609:
608:
583:(5038): 1643–7.
572:
566:
565:
554:
548:
547:
537:
505:
499:
498:
462:
456:
455:
419:
348:and the lack of
308:chemotherapeutic
21:
955:
954:
950:
949:
948:
946:
945:
944:
920:
919:
918:
873:
869:
824:
820:
775:
771:
724:
720:
675:
671:
616:
612:
573:
569:
556:
555:
551:
506:
502:
479:10.1038/nrc1669
463:
459:
420:
416:
412:
406:
395:
386:
378:dendritic cells
369:
367:Vaccine therapy
342:
337:
303:differentiation
292:spermatogenesis
290:. Also, during
284:
256:
235:
233:DNA methylation
223:DNA methylation
219:
209:cancers and in
148:
124:
33:are a group of
28:
23:
22:
15:
12:
11:
5:
953:
943:
942:
937:
932:
917:
916:
867:
818:
769:
718:
669:
610:
567:
549:
500:
457:
430:(188): 22–32.
413:
411:
408:
394:
391:
385:
382:
368:
365:
341:
340:Immunogenicity
338:
336:
333:
283:
280:
274:groups, while
255:
252:
234:
231:
218:
215:
147:
144:
123:
120:
63:bladder cancer
47:tumor antigens
26:
9:
6:
4:
3:
2:
952:
941:
938:
936:
933:
931:
928:
927:
925:
912:
908:
903:
898:
894:
890:
886:
882:
878:
871:
863:
859:
854:
849:
845:
841:
837:
833:
829:
822:
814:
810:
805:
800:
796:
792:
789:(2): 164–82.
788:
784:
780:
773:
765:
761:
756:
751:
746:
741:
737:
733:
729:
722:
714:
710:
705:
700:
696:
692:
689:(8): 1163–7.
688:
684:
680:
673:
665:
661:
656:
651:
646:
641:
637:
633:
630:(5): 1914–8.
629:
625:
621:
614:
606:
602:
598:
594:
590:
586:
582:
578:
571:
563:
559:
553:
545:
541:
536:
531:
527:
523:
520:(2): 164–82.
519:
515:
511:
504:
496:
492:
488:
484:
480:
476:
473:(8): 615–25.
472:
468:
461:
453:
449:
445:
441:
437:
433:
429:
425:
418:
414:
407:
404:
401:
390:
381:
379:
375:
364:
362:
357:
355:
354:immune system
351:
347:
332:
330:
326:
321:
318:
315:
313:
309:
304:
299:
297:
296:tumorigenesis
293:
289:
279:
277:
273:
270:(HAT) adding
269:
265:
261:
251:
248:
244:
240:
230:
228:
224:
214:
212:
208:
204:
200:
196:
192:
188:
184:
180:
175:
173:
169:
165:
161:
160:spermatocytes
157:
156:spermatogonia
152:
143:
141:
137:
133:
129:
119:
117:
113:
109:
105:
101:
97:
92:
90:
85:
83:
79:
78:spermatocytes
76:
75:spermatogonia
72:
71:Gametogenesis
68:
67:neuroblastoma
64:
60:
56:
52:
48:
44:
40:
36:
32:
19:
884:
880:
870:
835:
831:
821:
786:
782:
772:
735:
731:
721:
686:
682:
672:
627:
623:
613:
580:
576:
570:
562:CTA Database
561:
558:"CTDatabase"
552:
517:
513:
503:
470:
466:
460:
427:
423:
417:
405:
396:
387:
370:
358:
343:
322:
319:
316:
314:in cancers.
300:
285:
257:
239:methyl group
236:
220:
176:
153:
149:
125:
93:
86:
55:liver cancer
30:
29:
400:lymphocytes
260:nucleosomes
243:methylation
102:, MAGE-A4,
59:lung cancer
924:Categories
881:Oncotarget
832:Oncotarget
410:References
288:metastasis
82:spermatids
43:germ cells
312:phenotype
247:promoters
245:in their
217:Mechanism
940:Oncology
911:26158218
862:26158218
813:21376678
764:18838390
544:21376678
487:16034368
452:24718232
444:12445278
374:vaccines
361:peptides
282:Function
199:prostate
187:melanoma
164:pancreas
146:Category
140:placenta
132:melanoma
104:NY-ESO-1
51:melanoma
35:proteins
902:4599236
853:4599236
804:5528287
755:2686577
713:9547328
704:2212229
664:9050879
632:Bibcode
605:1840703
585:Bibcode
577:Science
535:5528287
495:2000946
329:mitosis
325:meiosis
227:histone
191:bladder
122:History
100:MAGE-A3
96:MAGE-A1
909:
899:
860:
850:
811:
801:
762:
752:
711:
701:
662:
652:
603:
542:
532:
493:
485:
450:
442:
272:acetyl
264:lysine
203:kidney
195:breast
179:RT-PCR
172:spleen
136:testis
930:Tumor
655:20017
491:S2CID
448:S2CID
207:colon
168:liver
108:PRAME
907:PMID
858:PMID
809:PMID
760:PMID
709:PMID
660:PMID
601:PMID
540:PMID
483:PMID
440:PMID
225:and
205:and
197:and
170:and
138:and
116:SSX2
114:and
112:CT83
87:The
80:and
897:PMC
889:doi
848:PMC
840:doi
799:PMC
791:doi
750:PMC
740:doi
699:PMC
691:doi
687:187
650:PMC
640:doi
593:doi
581:254
530:PMC
522:doi
475:doi
432:doi
428:188
926::
905:.
895:.
883:.
879:.
856:.
846:.
834:.
830:.
807:.
797:.
785:.
781:.
758:.
748:.
736:37
734:.
730:.
707:.
697:.
685:.
681:.
658:.
648:.
638:.
628:94
626:.
622:.
599:.
591:.
579:.
560:.
538:.
528:.
516:.
512:.
489:.
481:.
469:.
446:.
438:.
426:.
189:,
166:,
118:.
110:,
106:,
98:,
69:.
61:,
57:,
53:,
913:.
891::
885:6
864:.
842::
836:6
815:.
793::
787:5
766:.
742::
715:.
693::
666:.
642::
634::
607:.
595::
587::
564:.
546:.
524::
518:5
497:.
477::
471:5
454:.
434::
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.