tumor-specific antigen

• 腫瘍特異性抗原、腫瘍特異的抗原

WordNet

1. stated explicitly or in detail; "needed a specific amount"
2. a medicine that has a mitigating effect on a specific disease; "quinine is a specific for malaria"
3. (sometimes followed by `to'
4. being or affecting a disease produced by a particular microorganism or condition; used also of stains or dyes used in making microscope slides; "quinine is highly specific for malaria"; "a specific remedy"; "a specific stain is one having a specific affinity for particular structural elements"
5. relating to or distinguishing or constituting a taxonomic species; "specific characters"
6. any substance (as a toxin or enzyme) that stimulates an immune response in the body (especially the production of antibodies)
7. an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm

PrepTutorEJDIC

1. 《名詞の前にのみ用いて》『特定の』,一定の・『明確な』,明白な・(そのものに)『特有の』,独特の《+『to』+『名』》・〈C〉(…の)特効薬《+『for』+『名』》・《複数形で》明細,細部(details)
2. 抗原(生物の体内にはいって免疫体を作る物質)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/06/30 07:46:21」(JST)

wiki en

[Wiki en表示]

Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in the host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential candidates for use in cancer therapy. The field of cancer immunology studies such topics.

Mechanism of tumor antigenesis

Normal proteins in the body are not antigenic because of self-tolerance, a process in which self-reacting cytotoxic T lymphocytes (CTLs) and autoantibody-producing B lymphocytes are called "centrally" in primary lymphatic tissue (BM) and "peripherally" in secondary lymphatic tissue (mostly thymus for T-cells and spleen/lymph nodes for B cells). Thus any protein that is not exposed to the immune system triggers an immune response. This may include normal proteins that are well sequestered from the immune system, proteins that are normally produced in extremely small quantities, proteins that are normally produced only in certain stages of development, or proteins whose structure is modified due to mutation.

Classification of tumor antigens

Initially tumor antigens were broadly classified into two categories based on their pattern of expression: Tumor-Specific Antigens (TSA), which are present only on tumor cells and not on any other cell and Tumor-Associated Antigens (TAA), which are present on some tumor cells and also some normal cells.

This classification, however, is imperfect because many antigens thought to be tumor-specific turned out to be expressed on some normal cells as well. The modern classification of tumor antigens is based on their molecular structure and source.

Accordingly they can be classified as;

• Products of Mutated Oncogenes and Tumor Suppressor Genes
• Products of Other Mutated Genes
  • Overexpressed or Aberrantly Expressed Cellular Proteins
  • Tumor Antigens Produced by Oncogenic Viruses
  • Oncofetal Antigens
  • Altered Cell Surface Glycolipids and Glycoproteins
  • Cell Type-Specific Differentiation Antigens

Types

Any protein produced in a tumor cell that has an abnormal structure due to mutation can act as a tumor antigen. Such abnormal proteins are produced due to mutation of the concerned gene. Mutation of protooncogenes and tumor suppressors which lead to abnormal protein production are the cause of the tumor and thus such abnormal proteins are called tumor-specific antigens. Examples of tumor-specific antigens include the abnormal products of ras and p53 genes. In contrast, mutation of other genes unrelated to the tumor formation may lead to synthesis of abnormal proteins which are called tumor-associated antigens.

Other examples include tissue differentiation antigens, mutant protein antigens, oncogenic viral antigens, cancer-testis antigens and vascular or stromal specific antigens. Tissue differentiation antigens are those that are specific to a certain type of tissue. Mutant protein antigens are likely to be much more specific to cancer cells because normal cells shouldn't contain these proteins. Normal cells will display the normal protein antigen on their MHC molecules, whereas cancer cells will display the mutant version. Some viral proteins are implicated in forming cancer (oncogenesis), and some viral antigens are also cancer antigens. Cancer-testis antigens are antigens expressed primarily in the germ cells of the testes, but also in fetal ovaries and the trophoblast. Some cancer cells aberrantly express these proteins and therefore present these antigens, allowing attack by T-cells specific to these antigens. Example antigens of this type are CTAG1B and MAGEA1.

Proteins that are normally produced in very low quantities but whose production is dramatically increased in tumor cells, trigger an immune response. An example of such a protein is the enzyme tyrosinase, which is required for melanin production. Normally tyrosinase is produced in minute quantities but its levels are very much elevated in melanoma cells.

Oncofetal antigens are another important class of tumor antigens. Examples are alphafetoprotein (AFP) and carcinoembryonic antigen (CEA). These proteins are normally produced in the early stages of embryonic development and disappear by the time the immune system is fully developed. Thus self-tolerance does not develop against these antigens.

Abnormal proteins are also produced by cells infected with oncoviruses, e.g. EBV and HPV. Cells infected by these viruses contain latent viral DNA which is transcribed and the resulting protein produces an immune response.

In addition to proteins, other substances like cell surface glycolipids and glycoproteins may also have an abnormal structure in tumor cells and could thus be targets of the immune system.

Importance of tumor antigens

Tumor antigens, because of their relative abundance in tumor cells are useful in identifying specific tumor cells. Certain tumors have certain tumor antigens in abundance.

Tumor antigen	Tumor in which it is found	Remarks
Alphafetoprotein (AFP)	Germ cell tumors Hepatocellular carcinoma
Carcinoembryonic antigen (CEA)	Bowel cancers	Occasional lung or breast cancer
CA-125	Ovarian cancer
MUC-1	Breast cancer
Epithelial tumor antigen (ETA)	Breast cancer
Tyrosinase	Malignant melanoma	normally present in minute quantities; greatly elevated levels in melanoma
Melanoma-associated antigen (MAGE)	Malignant melanoma	Also normally present in the testis
abnormal products of ras, p53	Various tumors

Certain tumor antigens are thus used as tumor markers. More importantly, tumor antigens can be used in cancer therapy as tumor antigen vaccines.

See also

• Cancer immunotherapy

References

• Kumar, Abbas, Fausto; Robbins and Cotran: Pathologic Basis of Disease; Elsevier, 7th ed.
• Coulie PG, Hanagiri T, Takanoyama M: From Tumor Antigens to Immunotherapy. Int J Clin Oncol 6:163, 2001.

External links

• Chapter on tumor antigens in Cancer Medicine at NCBI

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 造血細胞移植後の再発の予防および治療のための免疫療法 immunotherapy for the prevention and treatment of relapse following hematopoietic cell transplantation
• 2. 胎児および新生児における免疫細胞の発達 the development of immune cells in the fetus and neonate
• 3. 複合免疫不全 combined immunodeficiencies
• 4. 分類不能型低ガンマグロブリン血症の病因 pathogenesis of common variable immunodeficiency
• 5. 周期性発熱症候群およびその他の自己炎症性疾患：概要 periodic fever syndromes and other autoinflammatory diseases an overview

English Journal

• Automated synthesis of [(18)F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models.

• Bouvet V1, Wuest M1, Jans HS1, Janzen N2, Genady AR2, Valliant JF2, Benard F3, Wuest F4.
• EJNMMI research.EJNMMI Res.2016 Dec;6(1):40. doi: 10.1186/s13550-016-0195-6. Epub 2016 May 4.
• BACKGROUND: Prostate-specific membrane antigen (PSMA) is frequently overexpressed and upregulated in prostate cancer. To date, various (18)F- and (68)Ga-labeled urea-based radiotracers for PET imaging of PSMA have been developed and entered clinical trials. Here, we describe an automated synthesis o
• PMID 27142881

• Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2.

• Vilhelmsson Timmermand O1, Larsson E2, Ulmert D3, Tran TA4, Strand S2.
• EJNMMI research.EJNMMI Res.2016 Dec;6(1):27. doi: 10.1186/s13550-016-0181-z. Epub 2016 Mar 17.
• BACKGROUND: Prostate cancer ranks as the second most lethal malignancy in the Western world. Previous targeting of prostate-specific antigen and human kallikrein-related peptidase 2, two related enzymes abundantly expressed in prostatic malignancies, with radioimmunoconjugates intended for diagnosti
• PMID 26983637

• Targeting of radiolabeled J591 antibody to PSMA-expressing tumors: optimization of imaging and therapy based on non-linear compartmental modeling.

• Fung EK1,2, Cheal SM3,4, Fareedy SB5, Punzalan B6, Beylergil V7,8, Amir J9, Chalasani S10, Weber WA11,12, Spratt DE13, Veach DR14, Bander NH15, Larson SM16,17,18, Zanzonico PB19,20, Osborne JR21,22.
• EJNMMI research.EJNMMI Res.2016 Dec;6(1):7. doi: 10.1186/s13550-016-0164-0. Epub 2016 Jan 22.
• BACKGROUND: We applied a non-linear immunokinetic model to quantitatively compare absolute antibody uptake and turnover in subcutaneous LNCaP human prostate cancer (PCa) xenografts of two radiolabeled forms of the humanized anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 ((12
• PMID 26801327

Japanese Journal

• Fas-Deficient Fully Allogeneic Dendritic Cells Administered Via an Intratumoral Injection Route Show Efficient Antitumor Effects in Murine models

• Okano Shinji,Kondoh Haruhiko,Toshima Takeo,Nakagawara Hidekazu,Yoshizumi Tomoharu,Soejima Yuji,Shirabe Ken,Harada Mamoru,Yoshikai Yasunobu,Maehara Yoshihiko,岡野 慎士,近藤 晴彦,戸島 剛男,中川原 英和,吉住 朋晴,副島 雄二,調 憲,原田 守,吉開 泰信,前原 喜彦,オカノ シンジ,コンドウ ハルヒコ,トシマ タケオ,ナカガワラ ヒデカズ,ヨシズミ トモハル,ソエジマ ユウジ,シラベ ケン,ハラダ マモル,ヨシカイ ヤスノブ,マエハラ ヨシヒコ
• 福岡医学雑誌 104(1), 15-26, 2013-01-25
• … Dendritic cell (DC)-based immunotherapy is a potent, active and specific cancer immunotherapy, as DCs are preferable professional APCs (pAPCs) that prime the tumor-associated antigen (TAA)-specific CD8^+ T-cell response. …
• NAID 120005227184

• キメラ抗原受容体 （CAR） 発現細胞傷害性T細胞 (CTL) を用いた次世代養子免疫療法の開発

• 中川 岳志,岡田 直貴,中川 晋作
• Drug Delivery System 28(1), 35-44, 2013
• 養子免疫療法は、癌患者より採取したCD8+ T細胞から腫瘍特異的な細胞傷害性T細胞 (CTL) を分化誘導し、再び患者へと移入することで癌の退縮および転移・再発抑制を図る自己細胞療法である。しかし、癌患者は免疫抑制状態に陥っているため、治療に十分な数の腫瘍特異的CTLを誘導することが困難である。この打開策として、キメラ抗原受容体 (CAR) を発現させたCTLを創製する手法の開発が進められている。 …
• NAID 130003368334

• Novel process of intrathymic tumor-immune tolerance through CCR2-mediated recruitment of Sirpα + dendritic cells: A murine model

• Baba Tomohisa,Badr M.E.S.,Tomaru Utano,Ishizu Akihiro,Mukaida Naofumi
• PLoS ONE 7(7), e41154, 2012-07-16
• … Immune surveillance system can detect more efficiently secretory tumor-specific antigens, which are superior as a target for cancer immunotherapy. … On the contrary, immune tolerance can be induced in the thymus when a tumor antigen is massively secreted into circulation. …
• NAID 120004419373

Related Links

• Tumor-specific antigen | definition of tumor-specific antigen ...

antigen [an´tĭ-jen] any substance capable, under appropriate conditions, of inducing a specific immune response and reacting with the products of that response; that is, with specific antibody or specifically sensitized T lymphocytes, or both.

• Tumor-specific antigen - definition of tumor-specific antigen ...

Three approaches to melanoma vaccines have been and/ or are being investigated: (1) injecting a tumor-specific antigen with adjuvant, resulting in random in vivo targeting of dendritic cells; (2) injecting dendritic cells generated ex vivo ...

Related Pictures

---

★リンクテーブル★

リンク元	「腫瘍マーカー」「腫瘍特異性抗原」「腫瘍特異的抗原」
関連記事	「specific」「tumor」「specific antigen」

「腫瘍マーカー」

　　[★]

英

tumor marker

同

生物学的腫瘍マーカー biological tumor marker、癌マーカー cancer marker、悪性腫瘍特異物質 tumor-specific antigen

---

肺癌の腫瘍マーカー

	陽性率(疾患があるときに陽性となる確率, 感度)
	肺癌					備考
		扁平上皮癌	腺癌	小細胞癌	その他の疾患
CYFRA21-1	57.5%*	70-80%/73.1%*	30-40%	30-40%	良性疾患:10-15%
SCC		○			子宮頸癌、食道癌、皮膚癌
CEA	40-50%		50-60%
SLX	70%*		0.4		肝硬変
NSE	10-30%			70-90%
proGRP				70-90%/65.1%*		NSEより上昇率が高く、特異性に優れる
KL-6		○			肺腺癌、膵癌、乳癌で40-50%。間質性肺炎の補助診断
無印：標準呼吸器病学 第1版 p.327。* 臨床検査学第32版 p.634

臨床応用されている腫瘍マーカー (LAB.630)

肝癌関連　AFP, AFP-L3%, PIVKA-II
膵癌ならびにその他の消化器癌　CEA, CA19-9, Dupan-2, CA50, Span-1
肺癌　CEA, sialyl Lex-i (SLX), SCC, SYFRA21-1, NSE, ProGRP
婦人科悪性腫痩
　子宮癌：SCC, CA125
　卵巣癌：CA125, AFP, CEA, CA19-9, GAT
　乳癌　：CA15-3, BCA225, CEA, NCC-ST-439
尿器科悪性腫壕
　前立腺痛：PSA(γ-Sm), PAP
　膀胱癌　：BTA, NMP22
　神経内分泌腫療　NSE
　広範な腫瘍に反応するマーカー
　　TPA, BFP, IAP

消化管悪性腫瘍マーカー

• CEA：胎児癌性蛋白。陽性率：(50-70%)大腸癌、胆道癌、膵癌。(40-60%)肺癌。(30-40%)胃癌。良性疾患でも上昇する(胆嚢炎、胆管炎、膵炎)。
• DU-PAN-2：2→3シアリルLec抗原を認識する抗体。陽性率：(70-80%)膵癌、(60-70%)胆道癌。Lea-b-の個体でも陽性になる。良性疾患でも上昇する(慢性肝炎、肝硬変、胆道炎症を伴う胆石症)。
• CA19-9：Leaの基本骨格にシアル酸が結合したもの。陽性率：(80-90%)膵癌。(70-80%)胆道癌。良性疾患でも上昇する((10-40%)閉塞性黄疸、慢性肝炎、肝硬変)。日本人の約7-10%に存在するフコース転移酵素が欠如したLea-b-の個体ではCA19-9は産生されない。
• SLX：Lexの基本骨格にシアル酸が結合したもの。陽性率：(高い)肺癌、卵巣癌。(50-60%)胆道癌、膵癌。

主な腫瘍マーカー CBT QB vol2 p.297

AFP	肝細胞癌、肝芽腫、卵黄脳腫瘍
CEA	消化器系の癌、肺癌、乳癌(腺癌の頻度が高く、臓器特異性は低い)
CA19-9	胆道系の癌、膵癌
CA125	卵巣癌
CA15-3	乳癌、卵巣癌
PIVKA-II	肝細胞癌
PSA	前立腺癌

組織型別に有用な腫瘍マーカー(NEWエッセンシャル産科学・婦人科学 第3版 p.236)

上皮性腫瘍
　漿液性腺癌: CA125 *1
　粘液性腺癌: CA19-9 *2, CA72-4, CEA
胚細胞腫瘍
　卵黄嚢腫瘍: AFP *3
　絨毛癌: hCG
　未分化胚細胞腫: LDH *4
　悪性転化を伴う成熟嚢胞性奇形腫(扁平上皮癌) : SCC
性索間質性腫瘍(ホルモン)
　顆粒膜細胞腫,莢膜細胞腫:工ストロゲン
　Sertoli-間質性腫瘍, Leydig細胞腫(門細胞腫) :テストステロン
*1　上皮性腫瘍中で最も有用.類内膜腺癌,明細胞腺癌でも陽性を示す.子宮内膜症,炎症,妊娠初期も軽度-中等度上昇
*2　成熟嚢胞性奇形腫で陽性を示すことがある
*3　胎芽性癌,混合性腔細胞腫療でも陽性を示す
*4　非特異的

also see →「生殖系チュートリアル症例2_プレゼン.ppt」

産婦人科において重要視される腫瘍マーカー

• CEA：子宮癌、卵巣癌、粘液性卵巣腫瘍

• 大腸粘膜で発現している糖タンパク質

• 癌患者の血清中の他に、胎児の消化管粘膜にも見いだされたことから命名された。
• 補助診断、治療のモニターとして使われる

• 臓器特異性、疾患特異性は高くない。

• 早期癌の診断には役立たない。

• AFP：卵黄嚢腫瘍

• 胎児期に肝臓および卵黄嚢で発現

• 肝細胞癌、肝細胞の再生局面で再び産生されるようになることがある

• 肝細胞癌、卵黄嚢腫瘍、肝芽腫の腫瘍マーカー、炎症性肝疾患における肝再生の指標

• CA19-9：卵巣癌、子宮体癌

• (腫瘍)細胞表面の糖蛋白に結合している糖鎖

• 癌の血行性転移を促進するらしい
• 正常の胆管・膵管上皮、唾液腺でも発現

• 早期癌での陽性率は低い。

• 補助診断、治療・再発のモニター

• CA125：卵巣癌(漿液性嚢胞腺癌、粘液性嚢胞腺癌)、子宮頚癌、子宮体癌

• ヒト培養卵巣癌細胞に見いだされた抗原

• 卵巣癌の腫瘍マーカーとして用いられる(陽性率60-80%)
• 組織型によって陽性率が異なる(漿液性嚢胞腺癌 > 粘液性嚢胞腺癌)

• 診断、治療効果の評価、再発のモニターなどに有用

• SCC

• 子宮頚部扁平上皮癌から精製された蛋白質
• 早期癌でも比較的高い陽性率を示し、経過観察にも有用である。
• 一般に扁平上皮の存在する部位に広範な重症疾患存在すれば血中のSCCは上昇しうる
• 皮膚表面、唾液中に大量に存在し、採血時に複数回穿刺する事などによるコンタミネーションの可能性があります。

• 子宮頚癌(扁平上皮癌)、腟扁平上皮癌、外陰癌

腫瘍マーカー　臓器別

OLM.372改変

(略)

「腫瘍特異性抗原」

　　[★]

英

tumor-specific antigen

関

腫瘍特異的抗原

「腫瘍特異的抗原」

　　[★]

英

tumor-specific antigen

関

腫瘍特異性抗原

「specific」

　　[★]

• adj.

• (～に関して)明確な、はっきりとした(exact precise)、具体的な(in, about)
• (比較)(限定)特定の(particular)、一定の(⇔general)
• (～に)特有の、独特の(to)
• (比較)(医学)(～に)渡航のある(for)。特殊な
• (生物)(生物)種の
• 医学)特異の
• (物理)比の。物質固有の。単位質量・長さ・面積・容積で

n.

関

specifically、specificity

　 　 　 　 　 　

「tumor」

　　[★]

• n.

• 腫瘍、腫瘤、腫脹

　

「specific antigen」

　　[★]

• 特異抗原、特異的抗原