In the current issue of the JCI, Poncette et al. used mice with human TCRαβ and HLA gene loci to discover CD4+ TCRs of optimal affinity for cancer testis antigen (CTA) NY-ESO-1.
Cancer vaccine trials based on CT antigens MAGE-A3 and NY-ESO-1 are currently ongoing, and these antigens may also play a role in antigen-specific adoptive T-cell transfer and in the immunomodulation approach of cancer therapy.
Indeed, these drugs not only trigger MPM cell death, but also induce the expression of cancer testis antigens recognized by CD8(+) T cells, such as New York-esophageal cancer-1 (NY-ESO-1).
We aimed to determine the effect of SGI-110 on methylation and expression of the cancer testis antigens (CTAs) NY-ESO-1 and MAGE-A in epithelial ovarian cancer (EOC) cells in vitro and in vivo and to establish the impact of SGI-110 on expression of major histocompatibility (MHC) class I and Intracellular Adhesion Molecule 1 (ICAM-1) on EOC cells, and on recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells.
The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out.
In the 79 lung cancer tissues, MAGE-3 (42%) was expressed most frequently and followed by NY-SAR-35 (33%), NY-ESO-1 (30%), MAGE-1 (27%), CT-7 (20%), MAGE-4 (19%), LAGE-1 (16%), and MAGE-10 (14%).
Typing of 33 non-small cell lung cancers for coexpression of a panel of CT antigens revealed a high incidence (60%) of MAGE-3 mRNA expression, followed by MAGE-1 (36%), CT7/MAGE-C1 (30%), CT10 (30%), SSX4 (23%), BRDT (21%), NY-ESO-1 (21%) and HOM-MEL-40/SSX2 (15%).
The aim of this study was to evaluate the prevalence of cancer testis tumor-associated antigens MAGE-A and NY-ESO-1 in cervical cancer and correlate expression patterns with clinicopathologic parameters and prognosis.
NY-ESO-1 is a cancer/testis (CT) antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers.
The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses.
Of 100 serum samples screened for CT antigen-specific antibodies, antibodies against NY-ESO-1 were detected in 4 patients, against SCP-1 in 6 patients and against SSX-2 in 1 patient, while no antibodies were detected against MAGE-3, CT-7 and CT-10.
To identify new CT antigens, we constructed an expression cDNA library from a melanoma cell line that expresses a wide range of CT antigens and screened the library with an allogeneic melanoma patient serum known to contain antibodies against two CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated from this library identified four CT antigen genes: MAGE-4a, NY-ESO-1, LAGE-1, and CT7.
Melanoma-associated antigen-A (MAGE-A) and New York esophageal squamous cell cancer-1 (NY-ESO-1) are 2 cancer testis antigens (CTA) demonstrating potential for use in targeted immunotherapy.
MAGE-A1, MAGE-A3, and NY-ESO-1 are cancer-testis (CT) antigens expressed on a number of malignant solid tumors, including neuroblastoma, but many tumor cell lines down-regulate the expression of CT antigens as well as major histocompatibility (MHC) antigens, precluding recognition by antigen-specific T cells.
Real-time RT-PCR analysis of newly defined CT genes and the prototype CT antigens, MAGE-3 and NY-ESO-1, revealed low levels (less than 3% of the level detected in testis) of CT15, CT16 and NY-ESO-1 in a limited range of normal, non-gametogenic tissues.
While all CT genes were frequently expressed in cell lines derived from pancreatic cancer, no expression of MAGE-3, SSX-1, SSX-2, NY-ESO-1 and CT-7 was detected in fresh tumor biopsies, and MAGE-4 (1/52), SSX-4 (1/39) and CT-8 (2/41) were only rarely expressed.
Notable examples include the dramatic benefit of chimeric antigen receptor gene-modified T cells redirected towards B-cell lineage antigen CD19 in patients with chronic lymphocytic leukemia, and the impressive outcomes in the use of TCR gene-modified T cells redirected towards NY-ESO-1, a representative cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma.