Cancer-testis antigens: An update on their roles in cancer immunotherapy

Abstract

BACKGROUND:

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.

Keywords

Cancer-testis antigen immunotherapy biomarker clinical trial

1. Background

Table 1
Summary of the clinical trials utilizing CTAs-based therapies in cancer patients (only currently recruiting studies are included, data have been obtained from https://clinicaltrials.gov)

Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
MAGE-A10 ${}^{c796}$ T cells	Lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion	Urothelial cancer, melanoma or head and neck cancers	HLA-A02:01 and HLA-A02:06 subjects	Treatment	I	No result posted
Anti-MAGE-A3-DP0401/0402 cells	Phase I experimental therapy: Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine $+$ Anti-MAGE-A3-DP4 TCR PBL $+$ high-dose aldeskin Phase II experimental therapy: Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine $+$ Anti-MAGE-A3-DP4 TCR PBL $+$ high-dose aldeskin	Cervical cancer, renal cancer, urothelial cancer, melanoma, breast	HLA-DP0401/0402 subjects	Treatment	I/II	No result posted
MAGE-A3/A6 T cell receptor engineered T cells (KITE-718)	Phase 1A: Cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, KITE-718. Phase 1B: Cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, KITE-718, at a dose selected based on Phase 1A	Solid tumor	HLA-DPB1*04:01 positive and whose tumors are MAGE-A3 and/or MAGE-A6 positive	Treatment	IA/IB	No result posted
MAGE-A4 ${}^{c1032}$ T cells	Infusion of autologous genetically modified MAGE-A4 ${}^{c1032}$ T on Day 1	Urinary bladder cancer, melanoma, head and neck cancer, ovarian cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, synovial sarcoma, myxoid round cell liposarcoma	HLA-A2 $+$ subjects with MAGE-A4 positive tumors	Treatment	I	No result posted
MG1 maraba/MAGE-A3 with and without adenovirus vaccine, with transgenic MAGE-A3	Patients may receive the Maraba virus, the adenovirus or both viruses	Advanced/metastatic solid tumors		Treatment	I/II	No result posted

Table 1, continued
Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab	MAGEA3 Intramuscular injection MG1-MAGEA3 intravenous infusion pembrolizumab intravenous infusion	Non-small cell lung cancer	Patients with incurable MAGE-A3-expressing solid tumors patients with non-small cell lung cancer: 1- who have completed a first standard therapy with at least 1 cycle of platinum based chemotherapy 2- at least one treatment of PD-1 or PD-L1 antibody targeted therapy	Treatment	I/II	No result posted
MAGE-A4 specific TCR gene transferred T lymphocytes	Following pre-treatment with cyclophosphamide and/or fludarabine, MAGE-A4-specific TCR gene transduced T lymphocytes	Solid tumors	HLA-A*24:02 positive patients	Treatment	I	No result posted
Oncolytic MG1 expressing MAGE-A3 (MG1-MAGEA3)	1-Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM), followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab 2-Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3, followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab	Metastatic melanoma, squamous cell skin carcinoma	Patients with previously treated metastatic melanoma or cutaneous squamous cell carcinoma	Treatment	Ib	No result posted
Peptide vaccine against long peptide sequences from NY-ESO-1, PRAME, MAGE-A3, WT-1	Azacitidine $+$ NPMW-peptide vaccine	Myelodysplastic syndrome, acute myeloid leukemia	Histologically confirmed high-risk MDS or AML	Treatment	I	No result posted
Genetically engineered PBMC and PBSC expressing NY-ESO-1 TCR	Administering NY-ESO-1 TCR (T cell receptor)engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after a myeloablative conditioning regimen	Locally advanced malignant neoplasm unresectable malignant neoplasm	HLA-A*0201 positive cells present/NY-ESO-1 positive	Treatment	I	No study results posted

Table 1, continued
Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
TBI-1301 (NY-ESO-1 Specific TCR gene transduced autologous T lymphocytes)	Genetically changed T cells will be given back to the subject through an intravenous infusion following cyclophosphamide pre-treatment	Synovial sarcoma melanoma esophageal cancer ovarian cancer lung cancer bladder cancer liver cancer	HLA-A02:01 or HLA-A02:06 positive patients	Treatment	I	No study results posted
TCR gene-engineered cells	Lymphodepleting conditioning followed by Infusion of Anti-NY ESO-1 Murine TCR-gene engineered lymphocytes	Melanoma meningioma breast cancer non-small cell lung cancer hepatocellular cancer	HLA-A*0201 positive	Treatment	II	No study results posted
NY-ESO-1 TCR engineered adoptive cell transfer therapy with Nivolumab PD-1 blockade	Gene-modified T cells, vaccine therapy, and nivolumab	Adult solid neoplasm childhood solid neoplasm metastatic neoplasm	HLA-A*0201 positive	Treatment	I	No study results posted
Targeted NY-ESO-1 T cell receptor (TCR) genetic modified autologous T cells	Targeted NY-ESO-1 T cell receptor (TCR) genetic modified autologous T cells treatment of advanced solid tumors	Advanced malignant solid tumors	NY-ESO-1 positive	Treatment	Not applicable	No study results posted
NY-ESO-1-specific T Cell Receptor	NY-ESO-1-specific TCR affinity enhancing specific T cell therapy (TAEST16001)	Liver cancer stage IV gastric cancer stage IV esophageal cancer, stage IV bone and soft tissue tumors breast cancer stage IV bladder carcinoma stage IV prostate carcinoma stage IV thyroid cancer stage IV ovarian cancer stage IV solid tumor	HLA-A*0201 $+$ and NY-ESO-1 positive cells $\geqslant$ 25%	Treatment	I	No study results posted
DEC-205/NY-ESO-1 fusion protein CDX-1401	IDO1 inhibitor INCB024360 in combination with DEC-205/NY-ESO-1 fusion protein CDX-1401 and adjuvant poly ICLC	Fallopian tube carcinoma ovarian carcinoma primary peritoneal carcinoma	Any human leukocyte antigen (HLA) type	Treatment	I/II	No study results posted

Table 2

Summary of the clinical trials utilizing CTAs-based therapies in cancer patients (only completed studies are included, data have been obtained from https://clinicaltrials.gov)

Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
RecMAGE-A3 protein $+$ AS15 adjuvant	Pre- and post-auto-SCT immunizations with recMAGE-A3 $+$ AS15	Multiple myeloma	MAGE-A3 tumor antigen expression subjects	Treatment	I	No result posted
MAGE-A3 $+$ HPV 16 vaccine	Three dose levels of MAGE-A3 vaccine and HPV-16 vaccine will be tested : 500 ug, 1000 ug and 1500 ug	Squamous cell carcinoma of the head and neck	Patients with HLA-A2 and MAGE-A3expression	Treatment	I	No result posted
Immunotherapeutic GSK2132231A (MAGE-A3 ASCI)	Receive intramuscularly up to 24 doses of MAGE-A3 ASCI in 4 cycles	Melanoma	MAGE-A3-positive patients	Treatment	II	Maximum 1-year OSR of any currently available treatment in the MAGE-A3-positive population $=$ 50%
MAGE-12 peptide vaccine	Patients receive MAGE-12 peptide vaccine emulsified in montanide ISA-51 adjuvant subcutaneously (SC) weekly for 4 doses	Lung, colorectal, bone, breast, eye cancer and sarcoma	HLA-Cw*0702 positive subjects and MAGE-12 expression patients	Treatment	I	No result posted
MAGE-A3 immunotherapy	Patients receiving peptide vaccinations as a shot just under the skin (subcutaneous) with DTPACE chemo and auto transplantation	Multiple myeloma	MAGE-A3 positive myeloma and are HLA-A0101 or -B35 positive will receive the MAGE-A3 peptide vaccine	Treatment	II/III	The peptides resulting in an immune response to myeloma. There is adverse effect like staphyloccocal infection in 75% of patients
recMAGE-A3 $+$ AS15 ASCI	Recombinant MAGE-A3 protein combined with AS15 immunological adjuvant system (recMAGE-A3 $+$ AS15) administered in two different administration sites, intramuscular (IM) or intradermal/subcutaneous (ID/SC)	Melanoma	Expression of MAGE-A3 by the tumor in patients	Treatment	Early phase I	The analysis determined the proportion of CD4 $+$ (and/or CD8 $+)$ T cells producing IFN-gamma or TNF $\alpha$ Treatment-related adverse events (AEs) were recorded
MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12	MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2	Metastatic melanoma	HLA-A2-positive patients will be eligible for screening	Treatment	II	No result posted
D1/3-MAGE-3-His fusion protein with SB-AS02B adjuvant	Patients receive D1/3-MAGE-3-His fusion protein emulsified in SB-AS02B adjuvant intramuscularly once every 3 weeks for a total of 12 weeks (4 injections)	Melanoma	MAGE-3 positive subject	Treatment	II	No result posted

Table 2, continued
Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
High dose interleukin-2 (HDIL-2) with recombinant MAGE-A3 protein combined with adjuvant system AS15 (recMAGE-A3 $+$ AS15)	720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. 300 $\mu$ g plus 420 $\mu$ g of CpG7909 (a part of the adjuvant system AS15) by intermuscular injection within 24 hours from first dose of HDIL-2	Metastatic melanoma	tumor tissue must be available for MAGE-A3 expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or liver lesion	Treatment	II	No result posted
MART-1 antigen $+$ recombinant MAGE-3.1 antigen $+$ recombinant interleukin $-$ 12	Melan-A peptide loaded PBMCs (sc, q3wk x 3), rhIL-12 (4 mcg, sc, days 1, 3 and 5 of every 3 wk cycle)	Metastatic melanoma	Patient must express HLA-A2 (a human leukocyte antigen) Tumor must express MAGE-3	Treatment	I/II	No result posted
Autologous dendritic cells loaded with MAGE-A3, MelanA and survivin	Patients received the vaccine intradermally; in cohort 2 the route of administration was intravenous Infusion	Melanoma (skin)	Histologically confirmed cutaneous* melanoma	Treatment	I/II	No result posted
Leuprolide $+$ GP100: 209–217(210M) Peptide $+$ MAGE-3 Peptide	1.0 ml subcutaneous injection in extremities	Melanoma	HLA-A *0201 positive	Prevention	II	No result posted
Melan-A analog peptide $+$ FluMa peptide $+$ Mage-A10 peptide $+$ SB AS-2 adjuvant $+$ Montanide adjuvant	Not provided	Melanoma	(HLA-A2) positive	Treatment	I	No result posted
NY-ESO-1 protein combined with CpG 7909	Vaccinations consisting of 100 $\mu$ g NY-ESO-1 protein combined with 2.5 mg CpG administered intradermally every 3 weeks for 4 doses	Prostate cancer	Patients with high-risk stage D1 or advanced prostate cancer	Treatment	I	No study results posted
NY-ESO-1 overlapping peptides	Repeated vaccination with NY-ESO-1 overlapping peptides (OLP4) with or without the immunoadjuvants Montanide and polyinosinic-polycytidylic acid – poly-L-lysine carboxymethylcellulose (poly-ICLC) administered every 3 weeks for a total of 5 vaccinations	Epithelial ovarian, fallopian tube, or primary peritoneal cancer	Cohort 1: 4 synthetic peptides coded by the NY-ESO-1 gene (i.e., NY-ESO-1 OLP4) once every 3 weeks for a total of 5 vaccinations Cohort 2: 4 synthetic peptides coded by the NY-ESO-1 gene (i.e., NY-ESO-1 OLP4) in combination with Montanide ISA-51 vegetable grade (VG) once every 3 weeks for a total of 5 vaccinations. Cohort 3: 4 synthetic peptides coded by the NY-ESO-1 gene (i.e., NY-ESO-1 OLP4) in combination with Montanide ISA-51 VG and poly-ICLC once every 3 weeks for a total of 5 vaccinations	Treatment	I	The AE reporting period for this study was up to 16 weeks for each subject

Table 2, continued
Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Result
NY-ESO-1-derived peptides or the NY-ESO-1 protein	Vaccination with CpG 7909 and montanide ISA 720 with or without cyclophosphamide in combination either with NY-ESO-1-derived peptides or the NY-ESO-1 Protein	NY-ESO-1-expressing tumors	Patient with NY-ESO-1 expression/No specific HLA expression required	Treatment	I	No study results posted
NY-ESO-1b peptide plus CpG 7909 and montanide ISA-51	Injection of the NY-ESO-1b peptide along with CpG 7909 and montanide ISA-51	Neoplasm	Patient with HLA-A2 phenotype whose tumor expresses the NY-ESO-1 or LAGE-1 antigen	Treatment	I	No study results posted
NY-ESO-1	Estimate the safety of NY-ESO-1 plasmid DNA (pPJV7611) cancer vaccine given by PMED	Prostate cancer bladder cancer non-small cell lung cancer esophageal cancer sarcoma	patients with tumor type known to express NY-ESO-1 or LAGE-1 antigen	Treatment	I	No study results posted
NY-ESO-1 protein with montanide and CpG 7909 as cancer vaccine	Vaccination with NY-ESO-1 recombinant protein mixed with CpG7909 and montanide ${}^{\@setsize{\scriptsize}{8pt}{\viipt}{\@viipt}\textregistered}$ ISA-51	Tumors	Patients with cancers that often express NY-ESO-1	Treatment	I	No study results posted
NY-ESO-1 protein vaccine	Immunization with complex of NY-ESO-1 protein and cholesterol-bearing Hydrophobized Pullulan (CHP)	Esophageal cancer	Patients with tumors expressing NY-ESO-1 or LAGE Antigen	Treatment	I	No study results posted
IMF-001 (recombinant NY-ESO-1 protein and cholesteryl hydrophobized pullulan )	Immunization of patients with IMF-001	Esophageal cancer	Patients with tumors expressing NY-ESO-1	Treatment	I	No study results posted
NY-ESO-1 peptide vaccine	NY-ESO-1b peptide vaccine and montanide ISA-51	Fallopian tube cancer ovarian cancer primary peritoneal cavity cancer	HLA-A2 positive	Treatment	I	No study results posted
NY-ESO-1/LAGE-1 HLA class I/II peptide vaccine	Immunotherapy using NY-ESO-1/LAGE1 peptide vaccine	Prostate cancer	Patients must be typed for HLA-DR4, DR13, DP4, or HLA-A2 haplotypes and matched HLA typing are eligible for vaccination regardless of initial NY-ESO-1 expression status	Treatment	I	No study results posted

Table 3

Summary of the withdrawn clinical trials utilizing CTAs-based therapies in cancer patients (data have been obtained from https://clinicaltrials. gov)

Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Cause of termination
RecMAGE-A3 $+$ AS15 ASCI $+$ Placebo	5 doses were administered (intramuscular) at 3-week intervals followed by 8 doses administered at 3-month intervals for a total maximum duration of study treatment administration of 27 months	Urinary bladder neoplasm	Urothelial carcinoma of the bladder which is MAGE-A3 positive	Prevention	II	Trial’s recruitment was prematurely stopped. The recMAGE-A3 $+$ AS15 patients were given the opportunity to continue treatment whereas placebo patients needed to stop treatment. All clinical data collected in this study were analysed descriptively
Anti-MAGE-A3/12 TCR-Gene engineered lymphocytes	PG13-MAGE-A3 TCR9W11 (anti-MAGE-A3/12 TCR) transduced autologous peripheral blood lymphocytes	Metastatic melanoma	Patients must be human leukocyte antigen (HLA)-A*0201 positive	Treatment	I/II	Not mentioned
T cell receptor immunotherapy targeting MAGE-A3	MAGE-A3-A1transduced PBL will be infused intravenously on the patient care unit over 20–30 minutes	Renal cancer breast cancer cervical cancer melanoma cancer	HLA-A*01 Positive	Treatment	I/II	Not mentioned
Recombinant MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK1203486A	GSK Biologicals’ Recombinant MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) GSK1203486A IM administration	Melanoma	The patient’s tumor shows expression of MAGE-A3 gene	Treatment	II	Not mentioned
MAGE-A1, MAGE-A3, and NY-ESO-1 vaccine	MAGE-A1, MAGE-A3, and NY-ESO-1 vaccine: A regimen of three vaccines every two weeks	Neuroblastoma rhabdomyosarcoma osteogenic sarcoma	Tumor is positive for NY-ESO-1, MAGE-A1, or MAGE-A3 by immunohistochemistry	Treatment	I	Not mentioned
NY-ESO-1 T cells	Leukapheresis, preconditioning chemotherapy with cyclophosphamide (60mg/kg) day $-$ 7 and day $-$ 6, followed by fludarabine (25 mg/m ${}^{2}$ ) day $-$ 5 to day $-$ 1, The NY-ESO-1 gene modified cells will be re-infused and the patients will receive up to 14 doses of intravenous Interleukin2 (100000 U/kg) from day 0 to day 4	Oesophageal cancer	NY-ESO-1 positive tumours and who are Human Leukocyte Antigen serotype “A” serotype group (HLA2) positive	Treatment	I	No study results posted withdrawal of funding

Table 3, continued
Immunogen	Intervention	Cancer type	Inclusion criteria	Primary purpose	Clinical trial phase	Cause of termination
NY-ESO 1 ( $+)$ IIIB, IV	Combination therapy with MPDL3280A and CDX-1401	Non-small cell lung cancer	NY-ESO 1 ( $+)$ IIIB, IV or recurrent non-small cell lung cancer	Treatment	II	No study results posted study closed due to lack of enrollment
Anti-NY ESO-1 T cell receptor (TCR) cluster of differentiation 62L (CD62L) $+$ engineered peripheral blood lymphocyte (PBL)	CD62L $+$ -derived T lymphocytes transduced with a T cell receptor recognizing the NY-ESO-1 antigen and aldesleukin following lymphodepletion	Metastatic melanoma	HLA-A*0201 positive	Treatment	II	Study was closed due to poor accrual
Modified white blood cells that secrete IL-2 and express a protein that targets the ESO-1 tumor Protein	Lymphodepleting conditioning followed by infusion of gene engineered lymphocytes cotransduced with genes encoding IL-12 and Anti-NY ESO-1 TCR	Metastatic melanoma metastatic renal cancer	HLA-A*0201 positive	Treatment	I	No study results posted not mentioned
NY-ESO-1 peptide vaccine	Combining NY-ESO-1 peptide vaccine therapy with sargramostim	Sarcoma	HLA-A2 allele for NY-ESO-1 peptides	Treatment	I	No study results posted departure of PI

Restricted expression of a group of antigens in gametogenic and tumor tissues has resulted in nomination of these antigens as cancer-testis antigens (CTAs) [1, 2]. Based on the unavailability of testis antigens for immune system [3], CTAs are suitable candidates for cancer immunotherapy [4, 5, 6, 7]. Although CTAs are expressed in the majority of tumor samples, studies have failed to find a single CTA with unanimous expression across all specimens [8]. The presence of immune responses against CTAs has been documented in cancer patients. For instance, Oka et al. have detected robust immune responses against the XAGE1 CTA in lung adenocarcinoma patients who had high disease stages. Notably, they found associations between humoral responses and good patients’ outcome [9]. Evaluation of CTAs whose expressions have been associated with good patients’ outcome has led to find associations between CTA expression and cytotoxic T cells infiltration in some kinds of cancer [10]. Although similarities have been detected between CTA roles in normal and tumoral tissues [11], some preliminary studies indicate that they might have different roles in the gametogenic and tumor tissues [12, 13]. They have been firstly detected in melanoma [14]. Subsequently, immunological responses against them have been recognized in various malignant situations [15, 16]. Moreover, numerous investigations have shown expressions of CTAs in almost all types of malignancies including solid tumors [17, 18, 19, 20] and blood cancers [21, 22, 23]. Some CTAs such as PAS domain containing 1 (PASD1) has been shown to induce autologous T-cell responses in blood cancer patients [24].

2. Methods

We searched PubMed, google scholar and specific websites that registers clinical trials with the key words “cancer-testis antigen”, “clinical trial”, “cancer” and “malignancy”.

3. Results

Several clinical trials have assessed efficacy of CTA-based immunotherapeutic approaches in cancer patients [7, 25, 26]. However, their application in pediatric cancer has been limited [27]. Different formulations have been used in the clinical trials [28]. For example, the whole protein with an appropriate adjuvant [29, 30], selected peptides [31, 32, 33], genetically engineered dendritic cells (DCs) [34, 35], cancer cell lysate-pulsed autologous DC [36] or capsid-mutant vector [37] have been applied in different settings. In breast cancer patients, combinations of some CTAs have been shown to induce immune response in a high number of patients [38]. A number of studies have been already recruiting patients to assess their response to these treatments. The results of other studies have been published. For instance, Fujita et al. have conducted a phase I clinical trial in patients with high stage breast cancer using five CTAs. They reported induction of specific cytotoxic T lymphocytes (CTLs) in the majority of patients [39]. Wada et al. have reported stimulation of NY-ESO-1 immunity and some desirable clinical results in esophageal cancer patients after immunotherapy with NY-ESO-1 recombinant protein [40]. Sadanaga et al. have vaccinated cancer patients with MAGE3-pulsed DCs and detected CTL responses and favorable clinical outcomes in a subset of patients [41]. Others have shown induction systemic immune response in melanoma patients after administration of imiquimod in addition to NY-ESO-1 vaccine [42]. Totally, two CTAs namely MAGE-A3 and NY-ESO-1 have been used more frequently than others in clinical trials [43, 44]. A phase II clinical trial in melanoma patients using a 12-peptide mix has reported induction of immune response in association with clinical effects in patients [45]. Bender et al. detected fast initiation of extensive NY-ESO-1 peptide specific immune responses following vaccination with the related peptide [46]. Davis et al. have detected both humoral and cellular responses against several NY-ESO-1 epitopes after vaccination with recombinant NY-ESO-1 protein in addition to ISCOMATRIX adjuvant [47]. Administration of NY-ESO-1b and Montanide has induced immune responses in ovarian cancer patients as well [48]. Another study in esophageal cancer patients showed acceptable safety, immunological responses and hopeful disease control degree after administration of a combination of three CTA-derived peptides [49]. A phase I clinical trial in patients with metastatic esophageal cancer demonstrated induction of plasmacytoid DCs and natural killer cells, and augmented concentrations of Interferon $\alpha$ [50].

Tables 1 and 2 summarize the clinical trials utilizing CTAs-based therapies in cancer patients. Table 3 gives a summary of clinical trials that have been withdrawn due to technical or clinical problems.

4. Discussion

CTAs have an acknowledged role in the diagnosis of human cancers [51] especially in residual diseases [23, 52]. Moreover, their expression on malignant cells with stem cell features potentiates them as treatment targets [53]. They have parallel functions in stem cell differentiation and tumorigenesis [54]. However, their expression in normal stem cells might limit their use as immunotherapeutic targets [55]. Several studies have aimed at identification of their potential as treatment targets in cell lines [56, 57, 58], animal models [59, 60], clinical samples [61, 62, 63] and clinical trials [64]. Targeting CTAs can enhance efficiency of other therapeutic methods as well [65]. Yet, expression of some previously named CTAs has been detected in normal tissues [66]. Consequently, caution should be taken in the attribution of genes to this group of tumor antigens. Immunotherapeutic modalities take advantage of antigens with more restricted expression in normal tissues [67]. Recent studies indicate that certain panels of CTAs can be used in diagnosis of cancer in tissue samples or body fluids [68, 69, 70]. Therefore, expression levels of these CTAs can be used in the follow-up of patients after treatments strategies. Based on the availability of different formulations of CTA-based vaccines, future researches should compare efficiency of these modalities. As current methods did not accomplish the whole aspects of an efficacious treatment strategy [71], this field is open for further investigations. Their applications in tumors arose from immune-privileged sites as well as tissues with high levels of immune tolerance have resulted in some promising outcomes [72, 73].

5. Conclusion

Application of CTAs in clinical trials has encountered some problems including lack of appropriate response, scarcity of appropriate candidates and adverse effects. So, comprehensive assessment of all confounding parameters is required before conduction of trials.

Footnotes

Conflict of interest

No conflict of interest.

References

Ghafouri-Fard

and Modarressi

M.H.

, Cancer-testis antigens: Potential targets for cancer immunotherapy, Arch Iran Med 12 (2009), 395–404.

Smith

S.M.

and Iwenofu

O.H.

, NY-ESO-1: A promising cancer testis antigen for sarcoma immunotherapy and diagnosis, Chinese Clinical Oncology 7 (2018).

Nishikawa

Maeda

Ishida

Gnjatic

Sato

Mori

Sugiyama

Ito

Fukumori

Utsunomiya

Inagaki

Old

L.J.

Ueda

and Sakaguchi

, Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma, Blood 119 (2012), 3097–3104.

Ghafouri-Fard

and Ghafouri-Fard

, Immunotherapy in nonmelanoma skin cancer, Immunotherapy 4 (2012), 499–510.

Liang

S.X.

and Fan

M.W.

, Immunotherapy for adenoid cystic carcinoma of salivary glands: Cancer/testis antigens and 5-aza-2’-deoxycytidine, Medical Hypotheses 73 (2009), 768–769.

Ghafouri-Fard

Seifi-Alan

Shamsi

and Esfandiary

, Immunotherapy in multiple myeloma using cancer-testis antigens, Iranian Journal of Cancer Prevention 8 (2015).

Mahmoud

A.M.

, Cancer testis antigens as immunogenic and oncogenic targets in breast cancer, Immunotherapy 10 (2018), 769–778.

Garcia-Soto

A.E.

Schreiber

Strbo

Ganjei-Azar

Miao

Koru-Sengul

Simpkins

Nieves-Neira

Lucci

and Podack

E.R.

, Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors, Gynecol Oncol 145 (2017), 413–419.

Oka

Kurose

Isobe

Fukuda

and Ohue

, Clinical significance of humoral immunity against XAGE1 cancer-testis antigen in lung adenocarcinoma, Journal of Clinical Oncology 36 (2018).

10.

da Silva

V.L.

Fonseca

A.F.

Fonseca

da Silva

T.E.

Coelho

A.C.

Kroll

J.E.

de Souza

J.E.S.

Stransky

de Souza

G.A.

and de Souza

S.J.

, Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis, Oncotarget 8 (2017), 92966–92977.

11.

Azizi

and Ghafouri-Fard

, Outer dense fiber proteins: Bridging between male infertility and cancer, Archives of Iranian Medicine (AIM) 20 (2017).

12.

Ghafouri-Fard

and Modarressi

M.H.

, Expression of splice variants of cancer-testis genes ODF3 and ODF4 in the testis of a prostate cancer patient, Genetics and Molecular Research 11 (2012), 3642–3648.

13.

Mansouri

Mostafie

Rezazadeh

Shahlaei

and Modarressi

M.H.

, New function of TSGA10 gene in angiogenesis and tumor metastasis: A response to a challengeable paradox, Hum Mol Genet 25 (2016), 233–244.

14.

Faramarzi

and Ghafouri-Fard

, Melanoma: A prototype of cancer-testis antigen-expressing malignancies, Immunotherapy 9 (2017), 1103–1113.

15.

Hanafusa

Mohamed

A.E.A.

Domae

Nakayama

and Ono

, Serological identification of Tektin5 as a cancer/testis antigen and its immunogenicity, Bmc Cancer 12 (2012).

16.

Jager

Unkelbach

Frei

Bert

Scanlan

M.J.

Jager

Old

L.J.

Chen

Y.T.

and Knuth

, 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 Immun 2 (2002), 5.

17.

Dianatpour

Mehdipour

Nayernia

Mobasheri

M.B.

Ghafouri-Fard

Savad

and Modarressi

M.H.

, Expression of testis specific genes TSGA10, TEX101 and ODF3 in breast cancer, Iran Red Crescent Med J 14 (2012), 722–726.

18.

Mobasheri

M.B.

Shirkoohi

and Modarressi

M.H.

, Cancer/testis OIP5 and TAF7L genes are up-regulated in breast cancer, Asian Pac J Cancer Prev 16 (2015), 4623–4628.

19.

Ghafouri-Fard

Ousati Ashtiani

Sabah Golian

Hasheminasab

S.M.

and Modarressi

M.H.

, Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer, Arch Med Res 41 (2010), 195–200.

20.

Ghafouri-Fard

Abbasi

Moslehi

Faramarzi

Taba Taba Vakili

Mobasheri

and Modarressi

, 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 Dermatology 162 (2010), 772–779.

21.

Ghafouri-Fard

Modarressi

M.H.

and Yazarloo

, Expression of testis-specific genes, TEX101 and ODF4, in chronic myeloid leukemia and evaluation of TEX101 immunogenicity, Annals of Saudi Medicine 32 (2012), 256–261.

22.

Hardwick

N.R.

Ingram

Farzaneh

Mufti

G.J.

and Guinn

, Identification of a novel cancer-testis antigen as a target for the immunotherapy of acute myeloid leukaemia (AML), British Journal of Haematology 145 (2009), 19–20.

23.

Mobasheri

M.B.

Modarressi

M.H.

Shabani

Asgarian

Sharifian

R.A.

Vossough

and Shokri

, Expression of the testis-specific gene, TSGA10, in Iranian patients with acute lymphoblastic leukemia (ALL), Leuk Res 30 (2006), 883–889.

24.

Guinn

Bland

E.A.

Lodi

Liggins

A.P.

Tobal

Petters

Wells

J.W.

Banham

A.H.

and Mufti

G.J.

, Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia, Biochemical and Biophysical Research Communications 335 (2005), 1293–1304.

25.

Faramarzi

and Ghafouri-Fard

, Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy, Immunotherapy 9 (2017), 1019–1034.

26.

Salmaninejad

Zamani

M.R.

Pourvahedi

Golchehre

Bereshneh

A.H.

and Rezaei

, Cancer/testis antigens: Expression, regulation, tumor invasion, and use in immunotherapy of cancers, Immunological Investigations 45 (2016), 619–640.

27.

Ghafouri-Fard

, Expression of cancer-testis antigens in pediatric cancers, Asian Pac J Cancer Prev 16 (2015), 5149–5152.

28.

Taherian-Esfahani

Abedin-Do

Nikpayam

Tasharofi

Nezamabadi

A.G.

and Ghafouri-Fard

, Cancer-testis antigens: A novel group of tumor biomarkers in ovarian cancers, Iranian Journal of Cancer Prevention 9 (2016).

29.

Vansteenkiste

J.F.

Cho

B.C.

Vanakesa

De Pas

Zielinski

Kim

M.S.

Jassem

Yoshimura

Dahabreh

Nakayama

Havel

Kondo

Mitsudomi

Zarogoulidis

Gladkov

O.A.

Udud

Tada

Hoffman

Bugge

Taylor

Gonzalez

E.E.

Liao

M.L.

Pujol

J.L.

Louahed

Debois

Brichard

Debruyne

Therasse

and Altorki

, 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 Oncol 17 (2016), 822–835.

30.

Kruit

W.H.

Suciu

Dreno

Mortier

Robert

Chiarion-Sileni

Maio

Testori

Dorval

Grob

J.J.

Becker

J.C.

Spatz

Eggermont

A.M.

Louahed

Lehmann

F.F.

Brichard

V.G.

and Keilholz

, 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 Oncol 31 (2013), 2413–2420.

31.

Germeau

Schiavetti

Lurquin

Henry

Vigneron

Brasseur

Lethe

De Plaen

Velu

Boon

and Coulie

P.G.

, High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens, J Exp Med 201 (2005), 241–248.

32.

Marchand

van Baren

Weynants

Brichard

Dreno

Tessier

M.H.

Rankin

Parmiani

Arienti

Humblet

Bourlond

Vanwijck

Lienard

Beauduin

Dietrich

P.Y.

Russo

Kerger

Masucci

Jager

De Greve

Atzpodien

Brasseur

Coulie

P.G.

van der Bruggen

and Boon

, 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 Cancer 80 (1999), 219–230.

33.

Schuler-Thurner

Dieckmann

Keikavoussi

Bender

Maczek

Jonuleit

Roder

Haendle

Leisgang

Dunbar

Cerundolo

von Den Driesch

Knop

Brocker

E.B.

Enk

Kampgen

and Schuler

, 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 Immunol 165 (2000), 3492–3496.

34.

Russo

Pilla

Lunghi

Crocchiolo

Greco

Ciceri

Maggioni

Fontana

Mukenge

Rivoltini

Rigamonti

Mercuri

S.R.

Nicoletti

Maschio

A.D.

Gianolli

Fazio

Marchiano

Florio

A.D.

Maio

Salomoni

Gallo-Stampino

Fiacco

M.D.

Lambiase

Coulie

P.G.

Patuzzo

Parmiani

Traversari

Bordignon

Santinami

and Bregni

, Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes, Int J Cancer 132 (2013), 2557–2566.

35.

Wilgenhof

Corthals

Heirman

van Baren

Lucas

Kvistborg

Thielemans

and Neyns

, Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma, J Clin Oncol 34 (2016), 1330–1338.

36.

Toh

H.C.

Wang

W.-W.

Chia

W.K.

Kvistborg

Sun

Teo

Phoon

Y.P.

Soe

Tan

S.H.

and Hee

S.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.

Batchu

R.B.

Gruzdyn

O.V.

Moreno-Bost

A.M.

Szmania

Jayandharan

Srivastava

Kolli

B.K.

Weaver

D.W.

van Rhee

and Gruber

S.A.

, Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector, Vaccine 32 (2014), 938–943.

38.

Ghafouri-Fard

Shamsi

Seifi-Alan

Javaheri

and Tabarestani

, Cancer-testis genes as candidates for immunotherapy in breast cancer, Immunotherapy 6 (2014), 165–179.

39.

Fujita

Yoshida

Nishimura

Koshikawa

Nagura

Yoshida

Miyoshi

Yamauchi

Nakamura

and Fujimori

, 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 Oncology 30 (2012), e13037–e13037.

40.

Wada

Sato

Uenaka

Isobe

Kawabata

Nakamura

Iwae

Yonezawa

Yamasaki

Miyata

Doki

Shiku

Jungbluth

A.A.

Ritter

Murphy

Hoffman

E.W.

Old

L.J.

Monden

and Nakayama

, Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination, Int J Cancer 123 (2008), 2362–2369.

41.

Sadanaga

Nagashima

Mashino

Tahara

Yamaguchi

Ohta

Fujie

Tanaka

Inoue

Takesako

Akiyoshi

and Mori

, Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas, Clinical Cancer Research 7 (2001), 2277–2284.

42.

Adams

O’Neill

D.W.

Nonaka

Hardin

Chiriboga

Siu

Cruz

C.M.

Angiulli

Ritter

Holman

R.M.

Shapiro

R.L.

Berman

R.S.

Berner

Shao

Manches

Pan

Venhaus

R.R.

Hoffman

E.W.

Jungbluth

Gnjatic

Old

Pavlick

A.C.

and Bhardwaj

, Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant, J Immunol 181 (2008), 776–784.

43.

Esfandiary

and Ghafouri-Fard

, MAGE-A3: An immunogenic target used in clinical practice, Immunotherapy 7 (2015), 683–704.

44.

Esfandiary

and Ghafouri-Fard

, New York esophageal squamous cell carcinoma-1 and cancer immunotherapy, Immunotherapy 7 (2015), 411–439.

45.

Slingluff

C.L.

Petroni

G.R.

Chianese-Bullock

K.A.

Smolkin

M.E.

Hibbitts

Murphy

Johansen

Grosh

W.W.

Yamshchikov

G.V.

Neese

P.Y.

Patterson

J.W.

Fink

and Rehm

P.K.

, Immunologic and clinical outcomes of a Randomized phase II trial of two multipeptide Vaccines for melanoma in the adjuvant setting, Clinical Cancer Research 13 (2007), 6386–6395.

46.

Bender

Karbach

Neumann

Jager

Al-Batran

S.E.

Atmaca

Weidmann

Biskamp

Gnjatic

Pan

Hoffman

Old

L.J.

Knuth

and Jager

, 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 Immun 7 (2007), 16.

47.

Davis

I.D.

Chen

Jackson

Parente

Shackleton

Hopkins

Chen

Dimopoulos

Luke

Murphy

Scott

A.M.

Maraskovsky

McArthur

MacGregor

Sturrock

Tai

T.Y.

Green

Cuthbertson

Maher

Miloradovic

Mitchell

S.V.

Ritter

Jungbluth

A.A.

Chen

Y.T.

Gnjatic

Hoffman

E.W.

Old

L.J.

and Cebon

J.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 A 101 (2004), 10697–10702.

48.

Diefenbach

C.S.

Gnjatic

Sabbatini

Aghajanian

Hensley

M.L.

Spriggs

D.R.

Iasonos

Lee

Dupont

Pezzulli

Jungbluth

A.A.

Old

L.J.

and Dupont

, 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 Res 14 (2008), 2740–2748.

49.

Kono

Mizukami

Daigo

Takano

Masuda

Yoshida

Tsunoda

Kawaguchi

Nakamura

and Fujii

, Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer, Cancer Sci 100 (2009), 1502–1509.

50.

Iwahashi

Katsuda

Nakamori

Nakamura

Naka

Ojima

Iida

and Yamaue

, 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 Sci 101 (2010), 2510–2517.

51.

Ghafouri-Fard

Nekoohesh

and Motevaseli

, Bladder cancer biomarkers: Review and update, Asian Pacific Journal of Cancer Prevention 15 (2014), 2395–2403.

52.

Ortmann

C.A.

Eisele

Nuckel

Klein-Hitpass

Fuhrer

Duhrsen

and Zeschnigk

, Aberrant hypomethylation of the cancer-testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia, Ann Hematol 87 (2008), 809–818.

53.

Tabarestani

and Ghafouri-Fard

, Cancer Stem Cells and Response to Therapy, Asian Pacific Journal of Cancer Prevention 13 (2012), 5947–5954.

54.

Gordeeva

, Cancer-testis antigens: Unique cancer stem cell biomarkers and targets for cancer therapy, Semin Cancer Biol 53 (2018), 75–89.

55.

Ghafouri-Fard

, Expression of cancer-testis antigens in stem cells: is it a potential drawback or an advantage in cancer immunotherapy, Asian Pac J Cancer Prev 16 (2015), 3079–3081.

56.

Azam

Ghafouri-Fard

Tabrizi

Modarressi

M.H.

Ebrahimzadeh-Vesal

Daneshvar

Mobasheri

M.B.

and Motevaseli

, 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 Prevention 15 (2014), 4255–4259.

57.

Ghafouri-Fard

Abdollahi

D.Z.

Omrani

and Azizi

, 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 Prevention 13 (2012), 5865–5869.

58.

Nouri

Neyazi

, Modarressi Karami

Abedin-Do

Taherian-Esfahani

Ghafouri-Fard

and Motevaseli

, 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 Onkol 31 (2018), 429–433.

59.

Chiriva-Internati

Mirandola

Jenkins

M.R.

Chapman

Cannon

Cobos

and Kast

W.M.

, Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer, PLoS One 5 (2010), e10471.

60.

Guo

Z.S.

Hong

J.A.

Irvine

K.R.

Chen

G.A.

Spiess

P.J.

Liu

Zeng

Wunderlich

J.R.

Nguyen

D.M.

and Restifo

N.P.

, De novo induction of a cancer/testis antigen by 5-aza-2’-deoxycytidine augments adoptive immunotherapy in a murine tumor model, Cancer Research 66 (2006), 1105–1113.

61.

Seifi-Alan

Shamsi

Ghafouri-Fard

Mirfakhraie

Zare-Abdollahi

Movafagh

Modarressi

M.H.

Kazemi

Geranpayeh

and Najafi-Ashtiani

, Expression Analysis of Two Cancer-testis Genes, FBXO39 and TDRD4, in Breast Cancer Tissues and Cell Lines, Asian Pacific Journal of Cancer Prevention 14 (2013), 6625–6629.

62.

Sani

S.A.

Forghanifard

M.M.

Sharifi

Bidokhti

M.H.

Bagherpoor

A.J.

and Abbaszadegan

M.R.

, Investigation of melanoma-associated antigen A4 cancer/testis antigen clinical relevance in esophageal squamous cell carcinoma, Journal of Cancer Research and Therapeutics 14 (2018), 1059–1064.

63.

Kazemi-Oula

Ghafouri-Fard

Mobasheri

M.B.

Geranpayeh

and Modarressi

M.H.

, Upregulation of RHOXF2 and ODF4 expression in breast cancer tissues, Cell Journal (Yakhteh) 17 (2015), 471.

64.

Lin

Wei

Chen

Huang

K.K.

and Zhang

, Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene, J Cancer Res Clin Oncol 140 (2014), 281–289.

65.

Ghafouri-Fard

and Ghafouri-Fard

, siRNA and cancer immunotherapy, Immunotherapy 4 (2012), 907–917.

66.

Ghafouri-Fard

Rezazadeh

Zare-Abdollahi

Omrani

M.D.

and Movafagh

, Are so-called cancer-testis genes expressed only in testis, Asian Pac J Cancer Prev 15 (2014), 7703–7705.

67.

Thomas

Al-Khadairi

Roelands

Hendrickx

Dermime

Bedognetti

and Decock

, NY-ESO-1 based immunotherapy of cancer: Current perspectives, Front Immunol 9 (2018), 947.

68.

Yazarlou

Kholghi-Oskooei

Afsharpad

Nekoohesh

Moharrami

Rad

H.M.

Ghafouri-Fard

and Modarressi

M.H.

, Expression analysis of a panel of cancer-testis antigens in bladder cancer, Per Med 15 (2018), 511–520.

69.

Yazarlou

Mowla

S.J.

Oskooei

V.K.

Motevaseli

Tooli

L.F.

Afsharpad

Nekoohesh

Sanikhani

N.S.

Ghafouri-Fard

and Modarressi

M.H.

, Urine exosome gene expression of cancer-testis antigens for prediction of bladder carcinoma, Cancer Manag Res 10 (2018), 5373–5381.

70.

Kulkarni

and Uversky

V.N.

, Cancer/testis antigens: “Smart” biomarkers for diagnosis and prognosis of prostate and other cancers, Int J Mol Sci 18 (2017).

71.

Zajac

Schultz-Thater

Tornillo

Sadowski

Trella

Mengus

Iezzi

and Spagnoli

G.C.

, MAGE-A antigens and cancer immunotherapy, Front Med (Lausanne) 4 (2017), 18.

72.

Ghafouri-Fard

and Modarressi

M.-H.

, Expression of cancer–testis genes in brain tumors: Implications for cancer immunotherapy, Immunotherapy 4 (2012), 59–75.

73.

Seifi-Alan

Shamsi

and Ghafouri-Fard

, Application of cancer-testis antigens in immunotherapy of hepatocellular carcinoma, Immunotherapy 10 (2018), 411–421.

Cancer-testis antigens: An update on their roles in cancer immunotherapy

Abstract

BACKGROUND:

OBJECTIVES:

METHODS:

RESULTS:

CONCLUSIONS:

Keywords

1. Background

Table 1 Summary of the clinical trials utilizing CTAs-based therapies in cancer patients (only currently recruiting studies are included, data have been obtained from https://clinicaltrials.gov)

3. Results

4. Discussion

5. Conclusion

Footnotes

Conflict of interest

References

Table 1
Summary of the clinical trials utilizing CTAs-based therapies in cancer patients (only currently recruiting studies are included, data have been obtained from https://clinicaltrials.gov)