Identification of a New Cancer/Germline Gene,<i>KK-LC-1</i>, Encoding an Antigen Recognized by Autologous CTL Induced on Human Lung Adenocarcinoma

Fukuyama, Takashi; Hanagiri, Takeshi; Takenoyama, Mitsuhiro; Ichiki, Yoshinobu; Mizukami, Makiko; So, Tetsuya; Sugaya, Masakazu; Saito, Tomoko; Sugio, Kenji; Yasumoto, Kosei

doi:10.1158/0008-5472.can-05-3840

Cited by 77 publications

(96 citation statements)

References 40 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TCRab gene was cloned from the HLA-B15-restricted CTL clone specific for KK-LC-1 (cancer/testis antigen), which was identified from a patient with lung adenocarcinoma. (9) The cloned TCRa and TCRb were then joined by a picornaviruslike 2A 'self-cleaving' peptide by overlapping PCR. The short 18 amino acid 2A sequence that separates the TCR a and TCR b results in equimolar expression of the TCRaand TCRbvia a 'ribosomal skip' mechanism.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Retracted: Antitumor activity of human γδ T cells transducted with CD8 and with T‐cell receptors of tumor‐specific cytotoxic T lymphocytes

et al. 2012

Self Cite

View full text Add to dashboard Cite

The difficulty in the induction and preparation of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of major problems in their application to adoptive immunotherapy. The present study tried to establish the useful antitumor effectors by using cd T cells through tumorspecific TCRab genes transduction, and evaluated the efficacy of their adoptive transfer in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice model. The TCRab gene was cloned from the HLA-B15-restricted CTL clone specific of the KitaKyushu Lung Cancer antigen-1 (KK-LC-1). The cloned TCRab as well as the CD8 gene were transduced into cd T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T lymphocyte activity was examined using a standard 4 h L ung cancer is the most common malignant neoplasm and the leading cause of cancer mortality in industrialized countries.(1) In spite of advances in diagnostic and therapeutic approaches against lung cancer, there has been limited improvement in treatment outcome. Recent clinical studies on immunotherapy indicate favorable therapeutic effects, and might become one of the alternative treatment approaches for lung cancer.(2-4) The adoptive transfer of tumor-infiltrating lymphocytes after the administration of lymphodepleting preparative regimen mediates objective cancer regression in 50% of patients with metastatic melanoma.(5) However, the difficulty in the induction and expansion of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of the major problems in their application to adoptive immunotherapy. To overcome this drawback, T-cell receptors (TCR) can be harnessed with antitumor specificities via molecular techniques. T-cell receptors with known antitumor reactivity can be genetically introduced into primary human T lymphocytes and provide effective tools for immunogenic therapy of tumors. (6) In contrast, human cd T cells can recognize and respond to a wide variety of stress-induced antigens, thereby developing innate broad antitumor and anti-infective activity.(7) These cells recognize antigens in a HLA complex-independent manner and develop strong cytolytic and Th1-like effector functions.(7) Furthermore, human cd T cells can be activated by phospho-antigens and aminobisphosphonates. Aminobisphosphonates also facilitate large-scale ex vivo expansion of functional cd T cells from the peripheral blood of cancer patients.(8) Although the antitumor effect is not antigen-specific cytotoxicity, cd T cells are attractive candidate effector cells for cancer immunotherapy.Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1) is a recently identified cancer/testis (CT) antigen from lung adenocarcinoma.(9) KK-LC-1 is a cancer/testis antigen because it is not expressed in normal tissues except for the testis, and is located on the X chromosome (Xq 22). A 9-mer peptide (KK-LC-1 76-84 ; RQKRILVNL) is recognized by CTL in a HLA B15-restricted manner. The present study tried to establish ...

show abstract

Section: Methodsmentioning

confidence: 99%

“…(9) KK-LC-1 is a cancer/testis antigen because it is not expressed in normal tissues except for the testis, and is located on the X chromosome (Xq 22). A 9-mer peptide (KK-LC-1 76-84 ; RQKRILVNL) is recognized by CTL in a HLA B15-restricted manner.…”

mentioning

confidence: 99%

Retracted: Antitumor activity of human γδ T cells transducted with CD8 and with T‐cell receptors of tumor‐specific cytotoxic T lymphocytes

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…KK-LC-1 therapy would be an attractive option for patients with TNBC because no existing hormone or antibody therapy is employed. KK-LC-1 has multiple epitope peptides recognized by cytotoxic T lymphocytes (CTLs) [22,23]. When CTLs against KK-LC-1 predominantly accumulate among tumorinfiltrating lymphocytes (TILs), adaptive immunotherapy using TILs leads to a good response [23].…”

Section: Kk-lc-1mentioning

confidence: 99%

Helicobacter Pylori Infection Induces Gastric Cancer and the Cancer/Testis Antigens Expression

Futawatari¹,

Fukuyama²,

Yamamura³

et al. 2017

J Infect Dis Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…In our autologous lymphocyte and tumor cell setting, seven tumor-associated antigens have been identifi ed in lung cancer, as shown in Table 2. 10,[20][21][22][23][24] Tumor associated antigens were generally classifi ed into fi ve categories: (1) cancer-testis (germline) antigen (C-T antigen); (2) melanocyte differentiation antigens; (3) amplifi cation or overexpression antigens; (4) tumorspecifi c mutated antigens; and (5) antigens encoded by oncogenic viruses. 25 C-T antigens (e.g., MAGE-1, MAGE-3, BAGE, GAGE, KK-LC-1, NY-ESO-1) are encoded by genes that are completely silent in most normal tissues but are activated in a number of tumors of various histological types.…”

Section: Tumor Antigens Identifi Ed In Lung Cancermentioning

confidence: 99%

“…KK-LC-1 was originally identifi ed from one of our patients with lung adenocarcinoma. 24 The KK-LC-1 coding gene is located on chromosome Xq22 and consists of 113 amino acids; the frequency of its expression in lung cancer tissues is 40% (adenocarcinoma 38%; squamous cell carcinoma 45%) and in lung cancer cell lines 50%. KK-LC-1 is also expressed in breast, esophageal, gastric, and colon cancers.…”

Section: Tumor Antigens Identifi Ed In Lung Cancermentioning

confidence: 99%

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

Yasumoto

Hanagiri

Takenoyama

2009

Gen Thorac Cardiovasc Surg

Self Cite

View full text Add to dashboard Cite

Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer.

show abstract

Identification of a New Cancer/Germline Gene,KK-LC-1, Encoding an Antigen Recognized by Autologous CTL Induced on Human Lung Adenocarcinoma

Cited by 77 publications

References 40 publications

Retracted: Antitumor activity of human γδ T cells transducted with CD8 and with T‐cell receptors of tumor‐specific cytotoxic T lymphocytes

Retracted: Antitumor activity of human γδ T cells transducted with CD8 and with T‐cell receptors of tumor‐specific cytotoxic T lymphocytes

Helicobacter Pylori Infection Induces Gastric Cancer and the Cancer/Testis Antigens Expression

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

Contact Info

Product

Resources

About