CTAG1B

Official Full Name

cancer/testis antigen 1B

Organism

Homo sapiens

GeneID

1485

Background

The protein encoded by this gene is an antigen that is overexpressed in many cancers but that is also expressed in normal testis. This gene is found in a duplicated region of the X-chromosome and therefore has a neighboring gene of identical sequence. [provided by RefSeq, Jan 2012]

Synonyms

CTAG; ESO1; CT6.1; CTAG1; LAGE-2; LAGE2B; NY-ESO-1;

Protein Sequence

MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRGPRGAGAARASGPGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEAELARRSLAQDAPPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLMWITQCFLPVFLAQPPSGQRR

Open

Disease

Esophageal cancer, Lung cancer, Melanoma, Multiple myeloma, Ovarian cancer, Solid tumour/cancer, Synovial sarcoma

Approved Drug

Clinical Trial Drug

7 +

Discontinued Drug

1 +

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Detailed Information

Cancer-testis antigens (CTAs) are special proteins found in tumors that are expressed in a specific way and could be useful for cancer treatment. The CTAG1B gene is an important part of the CTA family and plays a key role, particularly as a possible target for cancer treatment. The CTAG1B gene, also called the NY-ESO-1 gene, is found on the X chromosome in the q28 region. It makes a protein that is highly produced in many types of cancer but is hardly found in normal adult tissues. It mainly appears in germ cells like those in the testes. Tumor immunotherapy is advancing quickly, and using CTAG1B to focus this treatment has become a popular area of study.

Structure and Function of the CTAG1B Gene

The CTAG1B gene is 747bp in length and encodes a highly immunogenic protein, NY-ESO-1, which comprises 180 amino acids. The N-terminal of NY-ESO-1 is rich in glycine, while the C-terminal contains a conserved Pcc-1 domain. This structural characteristic suggests that NY-ESO-1 may play a significant role in cell cycle regulation and cell proliferation. Although NY-ESO-1 expression is very limited in normal adult tissues, confined mainly to reproductive cells like testes and the placenta, it shows high expression levels in various cancers, making it a potential tumor marker and target for immunotherapy.

Expression of CTAG1B in Tumors

Particularly in synovial sarcoma, myxoid liposarcoma, and neuroblastoma—where the expression levels are high—CTAG1B (NY-ESO-1) is markedly overexpressed in several solid malignancies. In particular, in myxoid and round-cell liposarcoma, NY-ESO-1 expresses itself between 89% and 100%. Furthermore, displaying varied degrees of positive expression in different malignancies including melanoma, ovarian cancer, and lung cancer, especially in metastatic tumors where its expression is tightly linked to tumor aggressiveness and prognosis, is NY-ESO-1.

However, the expression of NY-ESO-1 is often heterogeneous across various malignancies, therefore not all tumor cells always display this antigen. Targeted immunotherapy against NY-ESO-1 may therefore provide difficulties because of intra-tumor heterogeneity wherein certain cells do not express or have low expression of this antigen, thereby stressing the comprehensiveness and durability of therapeutic effects.

Immunogenicity of CTAG1B and Tumor Immunotherapy

With its great expression in tumors and immunogenicity, CTAG1B (NY-ESO-1) has grown to be a major target in tumor immunotherapy. Strong humoral and cellular immunological responses are possible from the NY-ESO-1 protein. Studies have shown that NY-ESO-1 may induce spontaneous immunological responses in tumor patients by activating certain cytotoxic T lymphocytes (CTLs) and helper T cell immune responses. These immune reactions not only identify and target tumor cells expressing NY-ESO-1 but also boost the immune system of the host.

Tumor vaccines based on NY-ESO-1 have grown to be an essential component of tumor immunotherapy in clinical settings. These vaccines especially provide NY-ESO-1 antigens or epitopes to induce T-cell immune reactions meant to find and destroy tumor cells. Each of the many forms of NY-ESO-1-targeted tumor vaccines—dendritic cell (DC), peptide, protein, viral vector, DNA, and mRNA—showcases unique benefits and drawbacks in preclinical and clinical studies.

For NY-ESO-1, for example, dendritic cell vaccines may improve the presenting capacity of dendritic cells, therefore triggering more robust T-cell immune responses. Direct delivery of peptide fragments including NY-ESO-1 epitopes by peptide vaccines improves T cell identification and assault on tumor cells much more. Furthermore, showing great possibilities are mRNA-based vaccinations, which activate the immune response and help the body of tumor patients synthesize NY-ESO-1 protein.

Even if these tumor vaccines show promise in clinical trials, the existence of tumor immune escape mechanisms usually reduces the efficacy of individual vaccination programs. Future studies should concentrate on overcoming obstacles of tumor immune escape and improving treatment effectiveness by combining NY-ESO-1 vaccines with other immunotherapeutic approaches, like as checkpoint inhibitors or adoptive cell therapy.

Preclinical Research and Clinical Application of CTAG1B

Research on CTAG1B (NY-ESO-1) has advanced to clinical stages. Early clinical trials demonstrated that NY-ESO-1-targeted immunotherapy could effectively activate T cell immune responses, especially displaying significant efficacy in synovial sarcoma and other tumors with high CTAG1B expression. Clinical data also indicate that NY-ESO-1 expression is closely associated with clinical tumor characteristics; tumors expressing NY-ESO-1 often show higher degrees of differentiation, lymph node metastasis, and progression in clinical staging. Therefore, NY-ESO-1 is not only a potential therapeutic target but may also serve as a prognostic marker for tumors.

Figure 1: Overview of NY-ESO-1 targeted cancer immunotherapy approaches, including vaccines, adoptive T cell therapy, and their combination with immune checkpoint inhibitors for effective tumor rejection. Figure 1. Overview of NY-ESO-1 targeted approaches for cancer immunotherapy. (Thomas R, et al., 2018)

In terms of therapeutic strategies, CTAG1B-targeted therapies are primarily implemented through vaccine immunotherapy and genetically engineered T-cell therapies, such as CAR-T cell therapy. Through genetic engineering, T cells can be modified to specifically recognize and attack NY-ESO-1-expressing tumor cells, a method validated in several clinical trials. Moreover, tumor vaccines, serving as a vital immunotherapy approach, help clear tumor cells by inducing specific immune responses, showing positive outcomes.

However, a major challenge for CTAG1B-targeted therapy is the heterogeneous expression of tumors, which may result in inadequate expression of NY-ESO-1 in some cells, affecting the efficacy of immunotherapy. Future research should focus on how combined treatment strategies or improved vaccine designs can enhance overall therapeutic effectiveness to overcome this issue.

References:

Thomas R, Al-Khadairi G, et al. NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives. Front Immunol. 2018 May 1;9:947.
Alsalloum A, Shevchenko JA, et al. NY-ESO-1 antigen: A promising frontier in cancer immunotherapy. Clin Transl Med. 2024 Sep;14(9):e70020.
Kurose K, Sakaeda K, et al. Immune checkpoint therapy and response biomarkers in non-small-cell lung cancer: Serum NY-ESO-1 and XAGE1 antibody as predictive and monitoring markers. Adv Clin Chem. 2023;112:155-204.

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