Several recent studies have assessed suitability of tumor antigens for immunotherapy. Based on the restricted expression pattern in somatic tissues, cancer-testis antigens (CTAs) are possible candidates for cancer immunotherapy. These antigens are expressed in various tumors including gastrointestinal, breast, skin and hematologic malignancies.
OBJECTIVES:
To find clinical trials utilizing CTAs in cancer patients.
METHODS:
We searched PubMed, google scholar and specific websites that registers clinical trials.
RESULTS:
A number of clinical trials have been designed to evaluate safety and efficacy of CTA-based treatments. The results of some of them have been promising. In the current literature search, we summarized the clinical trials of CTA-based therapies in cancer patients.
CONCLUSIONS:
Based on the availability of different formulations of CTA-based vaccines, future researches should compare efficiency of these modalities.
Ghafouri-FardS. and ModarressiM.H., Cancer-testis antigens: Potential targets for cancer immunotherapy, Arch Iran Med12 (2009), 395–404.
2.
SmithS.M. and IwenofuO.H., NY-ESO-1: A promising cancer testis antigen for sarcoma immunotherapy and diagnosis, Chinese Clinical Oncology7 (2018).
3.
NishikawaH.MaedaY.IshidaT.GnjaticS.SatoE.MoriF.SugiyamaD.ItoA.FukumoriY.UtsunomiyaA.InagakiH.OldL.J.UedaR. and SakaguchiS., Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma, Blood119 (2012), 3097–3104.
4.
Ghafouri-FardS. and Ghafouri-FardS., Immunotherapy in nonmelanoma skin cancer, Immunotherapy4 (2012), 499–510.
5.
LiangS.X. and FanM.W., Immunotherapy for adenoid cystic carcinoma of salivary glands: Cancer/testis antigens and 5-aza-2’-deoxycytidine, Medical Hypotheses73 (2009), 768–769.
6.
Ghafouri-FardS.Seifi-AlanM.ShamsiR. and EsfandiaryA., Immunotherapy in multiple myeloma using cancer-testis antigens, Iranian Journal of Cancer Prevention8 (2015).
7.
MahmoudA.M., Cancer testis antigens as immunogenic and oncogenic targets in breast cancer, Immunotherapy10 (2018), 769–778.
8.
Garcia-SotoA.E.SchreiberT.StrboN.Ganjei-AzarP.MiaoF.Koru-SengulT.SimpkinsF.Nieves-NeiraW.LucciJ. and PodackE.R., Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors, Gynecol Oncol145 (2017), 413–419.
9.
OkaM.KuroseK.IsobeM.FukudaM. and OhueY., Clinical significance of humoral immunity against XAGE1 cancer-testis antigen in lung adenocarcinoma, Journal of Clinical Oncology36 (2018).
10.
da SilvaV.L.FonsecaA.F.FonsecaM.da SilvaT.E.CoelhoA.C.KrollJ.E.de SouzaJ.E.S.StranskyB.de SouzaG.A. and de SouzaS.J., Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis, Oncotarget8 (2017), 92966–92977.
11.
AziziF. and Ghafouri-FardS., Outer dense fiber proteins: Bridging between male infertility and cancer, Archives of Iranian Medicine (AIM)20 (2017).
12.
Ghafouri-FardS.Ghafouri-FardS. and ModarressiM.H., Expression of splice variants of cancer-testis genes ODF3 and ODF4 in the testis of a prostate cancer patient, Genetics and Molecular Research11 (2012), 3642–3648.
13.
MansouriK.MostafieA.RezazadehD.ShahlaeiM. and ModarressiM.H., New function of TSGA10 gene in angiogenesis and tumor metastasis: A response to a challengeable paradox, Hum Mol Genet25 (2016), 233–244.
14.
FaramarziS. and Ghafouri-FardS., Melanoma: A prototype of cancer-testis antigen-expressing malignancies, Immunotherapy9 (2017), 1103–1113.
15.
HanafusaT.MohamedA.E.A.DomaeS.NakayamaE. and OnoT., Serological identification of Tektin5 as a cancer/testis antigen and its immunogenicity, Bmc Cancer12 (2012).
16.
JagerD.UnkelbachM.FreiC.BertF.ScanlanM.J.JagerE.OldL.J.ChenY.T. and KnuthA., Identification of tumor-restricted antigens NY-BR-1, SCP-1, and a new cancer/testis-like antigen NW-BR-3 by serological screening of a testicular library with breast cancer serum, Cancer Immun2 (2002), 5.
17.
DianatpourM.MehdipourP.NayerniaK.MobasheriM.B.Ghafouri-FardS.SavadS. and ModarressiM.H., Expression of testis specific genes TSGA10, TEX101 and ODF3 in breast cancer, Iran Red Crescent Med J14 (2012), 722–726.
18.
MobasheriM.B.ShirkoohiR. and ModarressiM.H., Cancer/testis OIP5 and TAF7L genes are up-regulated in breast cancer, Asian Pac J Cancer Prev16 (2015), 4623–4628.
19.
Ghafouri-FardS.Ousati AshtianiZ.Sabah GolianB.HasheminasabS.M. and ModarressiM.H., Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer, Arch Med Res41 (2010), 195–200.
20.
Ghafouri-FardS.AbbasiA.MoslehiH.FaramarziN.Taba Taba VakiliS.MobasheriM. and ModarressiM., Elevated expression levels of testis-specific genes TEX101 and SPATA19 in basal cell carcinoma and their correlation with clinical and pathological features, British Journal of Dermatology162 (2010), 772–779.
21.
Ghafouri-FardS.ModarressiM.H. and YazarlooF., Expression of testis-specific genes, TEX101 and ODF4, in chronic myeloid leukemia and evaluation of TEX101 immunogenicity, Annals of Saudi Medicine32 (2012), 256–261.
22.
HardwickN.R.IngramW.FarzanehF.MuftiG.J. and GuinnB., Identification of a novel cancer-testis antigen as a target for the immunotherapy of acute myeloid leukaemia (AML), British Journal of Haematology145 (2009), 19–20.
23.
MobasheriM.B.ModarressiM.H.ShabaniM.AsgarianH.SharifianR.A.VossoughP. and ShokriF., Expression of the testis-specific gene, TSGA10, in Iranian patients with acute lymphoblastic leukemia (ALL), Leuk Res30 (2006), 883–889.
24.
GuinnB.BlandE.A.LodiU.LigginsA.P.TobalK.PettersS.WellsJ.W.BanhamA.H. and MuftiG.J., Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia, Biochemical and Biophysical Research Communications335 (2005), 1293–1304.
25.
FaramarziS. and Ghafouri-FardS., Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy, Immunotherapy9 (2017), 1019–1034.
26.
SalmaninejadA.ZamaniM.R.PourvahediM.GolchehreZ.BereshnehA.H. and RezaeiN., Cancer/testis antigens: Expression, regulation, tumor invasion, and use in immunotherapy of cancers, Immunological Investigations45 (2016), 619–640.
27.
Ghafouri-FardS., Expression of cancer-testis antigens in pediatric cancers, Asian Pac J Cancer Prev16 (2015), 5149–5152.
28.
Taherian-EsfahaniZ.Abedin-DoA.NikpayamE.TasharofiB.NezamabadiA.G. and Ghafouri-FardS., Cancer-testis antigens: A novel group of tumor biomarkers in ovarian cancers, Iranian Journal of Cancer Prevention9 (2016).
29.
VansteenkisteJ.F.ChoB.C.VanakesaT.De PasT.ZielinskiM.KimM.S.JassemJ.YoshimuraM.DahabrehJ.NakayamaH.HavelL.KondoH.MitsudomiT.ZarogoulidisK.GladkovO.A.UdudK.TadaH.HoffmanH.BuggeA.TaylorP.GonzalezE.E.LiaoM.L.HeJ.PujolJ.L.LouahedJ.DeboisM.BrichardV.DebruyneC.TherasseP. and AltorkiN., Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet Oncol17 (2016), 822–835.
30.
KruitW.H.SuciuS.DrenoB.MortierL.RobertC.Chiarion-SileniV.MaioM.TestoriA.DorvalT.GrobJ.J.BeckerJ.C.SpatzA.EggermontA.M.LouahedJ.LehmannF.F.BrichardV.G. and KeilholzU., Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: Results of a randomized phase ii study of the european organisation for research and treatment of cancer melanoma group in Metastatic Melanoma, J Clin Oncol31 (2013), 2413–2420.
31.
GermeauC.MaW.SchiavettiF.LurquinC.HenryE.VigneronN.BrasseurF.LetheB.De PlaenE.VeluT.BoonT. and CoulieP.G., High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens, J Exp Med201 (2005), 241–248.
32.
MarchandM.van BarenN.WeynantsP.BrichardV.DrenoB.TessierM.H.RankinE.ParmianiG.ArientiF.HumbletY.BourlondA.VanwijckR.LienardD.BeauduinM.DietrichP.Y.RussoV.KergerJ.MasucciG.JagerE.De GreveJ.AtzpodienJ.BrasseurF.CoulieP.G.van der BruggenP. and BoonT., Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1, Int J Cancer80 (1999), 219–230.
33.
Schuler-ThurnerB.DieckmannD.KeikavoussiP.BenderA.MaczekC.JonuleitH.RoderC.HaendleI.LeisgangW.DunbarR.CerundoloV.von Den DrieschP.KnopJ.BrockerE.B.EnkA.KampgenE. and SchulerG., Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells, J Immunol165 (2000), 3492–3496.
34.
RussoV.PillaL.LunghiF.CrocchioloR.GrecoR.CiceriF.MaggioniD.FontanaR.MukengeS.RivoltiniL.RigamontiG.MercuriS.R.NicolettiR.MaschioA.D.GianolliL.FazioF.MarchianoA.FlorioA.D.MaioM.SalomoniM.Gallo-StampinoC.FiaccoM.D.LambiaseA.CoulieP.G.PatuzzoR.ParmianiG.TraversariC.BordignonC.SantinamiM. and BregniM., Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes, Int J Cancer132 (2013), 2557–2566.
35.
WilgenhofS.CorthalsJ.HeirmanC.van BarenN.LucasS.KvistborgP.ThielemansK. and NeynsB., Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma, J Clin Oncol34 (2016), 1330–1338.
36.
TohH.C.WangW.-W.ChiaW.K.KvistborgP.SunL.TeoK.PhoonY.P.SoeY.TanS.H. and HeeS.W., Clinical benefit of allogeneic melanoma cell lysate-pulsed autologous dendritic cell vaccine in MAGE-positive colorectal cancer patients, Clinical Cancer Research (2009), 1078–0432. CCR-09-1537.
37.
BatchuR.B.GruzdynO.V.Moreno-BostA.M.SzmaniaS.JayandharanG.SrivastavaA.KolliB.K.WeaverD.W.van RheeF. and GruberS.A., Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector, Vaccine32 (2014), 938–943.
38.
Ghafouri-FardS.ShamsiR.Seifi-AlanM.JavaheriM. and TabarestaniS., Cancer-testis genes as candidates for immunotherapy in breast cancer, Immunotherapy6 (2014), 165–179.
39.
FujitaT.YoshidaA.NishimuraH.KoshikawaK.NaguraN.YoshidaK.MiyoshiY.YamauchiH.NakamuraS.NakamuraY. and FujimoriM., Phase I clinical trial of multi-antigen peptide vaccines therapy using cancer-testis antigens for patients with advanced or recurrent breast cancer, Journal of Clinical Oncology30 (2012), e13037–e13037.
40.
WadaH.SatoE.UenakaA.IsobeM.KawabataR.NakamuraY.IwaeS.YonezawaK.YamasakiM.MiyataH.DokiY.ShikuH.JungbluthA.A.RitterG.MurphyR.HoffmanE.W.OldL.J.MondenM. and NakayamaE., Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination, Int J Cancer123 (2008), 2362–2369.
41.
SadanagaN.NagashimaH.MashinoK.TaharaK.YamaguchiH.OhtaM.FujieT.TanakaF.InoueH.TakesakoK.AkiyoshiT. and MoriM., Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas, Clinical Cancer Research7 (2001), 2277–2284.
42.
AdamsS.O’NeillD.W.NonakaD.HardinE.ChiribogaL.SiuK.CruzC.M.AngiulliA.AngiulliF.RitterE.HolmanR.M.ShapiroR.L.BermanR.S.BernerN.ShaoY.ManchesO.PanL.VenhausR.R.HoffmanE.W.JungbluthA.GnjaticS.OldL.PavlickA.C. and BhardwajN., Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant, J Immunol181 (2008), 776–784.
43.
EsfandiaryA. and Ghafouri-FardS., MAGE-A3: An immunogenic target used in clinical practice, Immunotherapy7 (2015), 683–704.
44.
EsfandiaryA. and Ghafouri-FardS., New York esophageal squamous cell carcinoma-1 and cancer immunotherapy, Immunotherapy7 (2015), 411–439.
45.
SlingluffC.L.PetroniG.R.Chianese-BullockK.A.SmolkinM.E.HibbittsS.MurphyC.JohansenN.GroshW.W.YamshchikovG.V.NeeseP.Y.PattersonJ.W.FinkR. and RehmP.K., Immunologic and clinical outcomes of a Randomized phase II trial of two multipeptide Vaccines for melanoma in the adjuvant setting, Clinical Cancer Research13 (2007), 6386–6395.
46.
BenderA.KarbachJ.NeumannA.JagerD.Al-BatranS.E.AtmacaA.WeidmannE.BiskampM.GnjaticS.PanL.HoffmanE.OldL.J.KnuthA. and JagerE., LUD 00-009: phase 1 study of intensive course immunization with NY-ESO-1 peptides in HLA-A2 positive patients with NY-ESO-1-expressing cancer, Cancer Immun7 (2007), 16.
47.
DavisI.D.ChenW.JacksonH.ParenteP.ShackletonM.HopkinsW.ChenQ.DimopoulosN.LukeT.MurphyR.ScottA.M.MaraskovskyE.McArthurG.MacGregorD.SturrockS.TaiT.Y.GreenS.CuthbertsonA.MaherD.MiloradovicL.MitchellS.V.RitterG.JungbluthA.A.ChenY.T.GnjaticS.HoffmanE.W.OldL.J. and CebonJ.S., Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans, Proc Natl Acad Sci U S A101 (2004), 10697–10702.
48.
DiefenbachC.S.GnjaticS.SabbatiniP.AghajanianC.HensleyM.L.SpriggsD.R.IasonosA.LeeH.DupontB.PezzulliS.JungbluthA.A.OldL.J. and DupontJ., Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission, Clin Cancer Res14 (2008), 2740–2748.
49.
KonoK.MizukamiY.DaigoY.TakanoA.MasudaK.YoshidaK.TsunodaT.KawaguchiY.NakamuraY. and FujiiH., Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer, Cancer Sci100 (2009), 1502–1509.
50.
IwahashiM.KatsudaM.NakamoriM.NakamuraM.NakaT.OjimaT.IidaT. and YamaueH., Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma, Cancer Sci101 (2010), 2510–2517.
51.
Ghafouri-FardS.NekooheshL. and MotevaseliE., Bladder cancer biomarkers: Review and update, Asian Pacific Journal of Cancer Prevention15 (2014), 2395–2403.
52.
OrtmannC.A.EiseleL.NuckelH.Klein-HitpassL.FuhrerA.DuhrsenU. and ZeschnigkM., Aberrant hypomethylation of the cancer-testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia, Ann Hematol87 (2008), 809–818.
53.
TabarestaniS. and Ghafouri-FardS., Cancer Stem Cells and Response to Therapy, Asian Pacific Journal of Cancer Prevention13 (2012), 5947–5954.
54.
GordeevaO., Cancer-testis antigens: Unique cancer stem cell biomarkers and targets for cancer therapy, Semin Cancer Biol53 (2018), 75–89.
55.
Ghafouri-FardS., Expression of cancer-testis antigens in stem cells: is it a potential drawback or an advantage in cancer immunotherapy, Asian Pac J Cancer Prev16 (2015), 3079–3081.
56.
AzamR.Ghafouri-FardS.TabriziM.ModarressiM.H.Ebrahimzadeh-VesalR.DaneshvarM.MobasheriM.B. and MotevaseliE., Lactobacillus acidophilus and lactobacillus crispatus culture supernatants downregulate expression of cancer-testis genes in the MDA-MB-231 cell line, Asian Pacific Journal of Cancer Prevention15 (2014), 4255–4259.
57.
Ghafouri-FardS.AbdollahiD.Z.OmraniM. and AziziF., shRNA mediated RHOXF1 silencing influences expression of BCL2 but not CASP8 in MCF-7 and MDA-MB-231 cell lines, Asian Pacific Journal of Cancer Prevention13 (2012), 5865–5869.
58.
NouriZ.NeyaziN., ModarressiKaramiF.Abedin-DoA.Taherian-EsfahaniZ.Ghafouri-FardS. and MotevaseliE., Down-regulation of TSGA10, AURKC, OIP5 and AKAP4 genes by Lactobacillus rhamnosus GG and Lactobacillus crispatus SJ-3C-US supernatants in HeLa cell line, Klin Onkol31 (2018), 429–433.
59.
Chiriva-InternatiM.YuY.MirandolaL.JenkinsM.R.ChapmanC.CannonM.CobosE. and KastW.M., Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer, PLoS One5 (2010), e10471.
60.
GuoZ.S.HongJ.A.IrvineK.R.ChenG.A.SpiessP.J.LiuY.ZengG.WunderlichJ.R.NguyenD.M. and RestifoN.P., De novo induction of a cancer/testis antigen by 5-aza-2’-deoxycytidine augments adoptive immunotherapy in a murine tumor model, Cancer Research66 (2006), 1105–1113.
61.
Seifi-AlanM.ShamsiR.Ghafouri-FardS.MirfakhraieR.Zare-AbdollahiD.MovafaghA.ModarressiM.H.KazemiG.GeranpayehL. and Najafi-AshtianiM., Expression Analysis of Two Cancer-testis Genes, FBXO39 and TDRD4, in Breast Cancer Tissues and Cell Lines, Asian Pacific Journal of Cancer Prevention14 (2013), 6625–6629.
62.
SaniS.A.ForghanifardM.M.SharifiN.BidokhtiM.H.BagherpoorA.J. and AbbaszadeganM.R., Investigation of melanoma-associated antigen A4 cancer/testis antigen clinical relevance in esophageal squamous cell carcinoma, Journal of Cancer Research and Therapeutics14 (2018), 1059–1064.
63.
Kazemi-OulaG.Ghafouri-FardS.MobasheriM.B.GeranpayehL. and ModarressiM.H., Upregulation of RHOXF2 and ODF4 expression in breast cancer tissues, Cell Journal (Yakhteh)17 (2015), 471.
64.
LinL.WeiJ.ChenY.HuangA.LiK.K. and ZhangW., Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene, J Cancer Res Clin Oncol140 (2014), 281–289.
65.
Ghafouri-FardS. and Ghafouri-FardS., siRNA and cancer immunotherapy, Immunotherapy4 (2012), 907–917.
66.
Ghafouri-FardS.RezazadehF.Zare-AbdollahiD.OmraniM.D. and MovafaghA., Are so-called cancer-testis genes expressed only in testis, Asian Pac J Cancer Prev15 (2014), 7703–7705.
67.
ThomasR.Al-KhadairiG.RoelandsJ.HendrickxW.DermimeS.BedognettiD. and DecockJ., NY-ESO-1 based immunotherapy of cancer: Current perspectives, Front Immunol9 (2018), 947.
68.
YazarlouF.Kholghi-OskooeiV.AfsharpadM.NekooheshL.MoharramiT.RadH.M.Ghafouri-FardS. and ModarressiM.H., Expression analysis of a panel of cancer-testis antigens in bladder cancer, Per Med15 (2018), 511–520.
69.
YazarlouF.MowlaS.J.OskooeiV.K.MotevaseliE.TooliL.F.AfsharpadM.NekooheshL.SanikhaniN.S.Ghafouri-FardS. and ModarressiM.H., Urine exosome gene expression of cancer-testis antigens for prediction of bladder carcinoma, Cancer Manag Res10 (2018), 5373–5381.
70.
KulkarniP. and UverskyV.N., Cancer/testis antigens: “Smart” biomarkers for diagnosis and prognosis of prostate and other cancers, Int J Mol Sci18 (2017).
71.
ZajacP.Schultz-ThaterE.TornilloL.SadowskiC.TrellaE.MengusC.IezziG. and SpagnoliG.C., MAGE-A antigens and cancer immunotherapy, Front Med (Lausanne)4 (2017), 18.
72.
Ghafouri-FardS. and ModarressiM.-H., Expression of cancer–testis genes in brain tumors: Implications for cancer immunotherapy, Immunotherapy4 (2012), 59–75.
73.
Seifi-AlanM.ShamsiR. and Ghafouri-FardS., Application of cancer-testis antigens in immunotherapy of hepatocellular carcinoma, Immunotherapy10 (2018), 411–421.
