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克隆號(hào)為H09的IDH1（isocitrate dehydrogenase 1, 異檸檬酸鹽脫氫酶1）鼠單克隆抗體為Dianova公司近期推出的產(chǎn)品之一，此抗體可特異性的檢測(cè)腦組織腫瘤中IDH1基因的R132H點(diǎn)突變。IDH1基因的第132密碼子的雜合突變是II 和III級(jí)神經(jīng)膠質(zhì)瘤（根據(jù)WHO的腫瘤學(xué)分類）的頻發(fā)事件。在大約70％的星形膠質(zhì)細(xì)胞瘤和少突神經(jīng)膠質(zhì)細(xì)胞瘤可發(fā)現(xiàn)IDH1基因的R132H點(diǎn)突變。

IDH1基因R132H突變?cè)诓糠帜X腫瘤中的頻發(fā)現(xiàn)象使克隆號(hào)為H09的IDH1抗體可高靈敏性和高特異性的用于此類腫瘤的鑒別診斷中：如從原發(fā)性膠質(zhì)母細(xì)胞瘤中區(qū)分出間變性星形細(xì)胞瘤、從毛細(xì)胞型星形細(xì)胞瘤或室管膜（細(xì)胞）瘤中區(qū)分出彌漫性星形細(xì)胞瘤（WHO分類II級(jí)），也可以用于具有IDH1突變的腫瘤細(xì)胞浸潤(rùn)前沿的與反應(yīng)性神經(jīng)膠質(zhì)增多癥的區(qū)分。因此，由于其高靈敏性和高特異性，此抗體在腦部腫瘤的分類分級(jí)中以及在檢測(cè)單一或少量浸潤(rùn)腫瘤細(xì)胞時(shí)是非常有用的。

DIA-PD1-P01 – Anti-PD-1 (Hu) aus Maus (Klon: NAT105) – unkonj. – 100 µl

Art.-Nr.                           DIA-PD1-P01

Spezifität                         PD-1

Spezies-Reaktivität                Human

Wirtsspezies                       Maus

Isotyp                             IgG1

Klon                               NAT105

Klonalität (Mono-/Polyklonal)      monoklonal

Anwendung                          Gefrierschnitte (IHC-F)

                                   Durchflusszytometrie (Flow Cytometry)
                                   Immunpräzipitation
                                   Immuncytochemie
                                   Immunhistochemie (IHC)
                                   Immunhistochemie (Paraffingewebe)
                                   Western Blot

Konjugation                        unkonjugiert

Verdünnung                         Histo-/Zytochemie 1:100

Format                             Lyophilisat

                                  gereinigter Antikörper (aus Kulturüberstand)

Produktlinie / Thema               Immunhistochemie

                                   Tumormarker/-biologie

Zweckbestimmung                     nur für Forschungszwecke

Suchcode                            DIAPD1

                                    PD-1
                                    NAT105
                                    FFPE
                                    Paraffin

Hersler / Marke                  dianova

Background

PD-1 (Programmed Cell-Death 1) is expressed by germinal center-associated T cells in reactive lymphoid tissue. PD-1(CD279, PDCD1, SLEB2) plays a key role in peripheral tolerance and autoimmune disease. Several tumors express ligand for PD1 (PDL1). On binding activated T cells in the tumor microenvironment, PD-1 inactivates antigen specific T cells that would other-wise attack tumor cells. Monoclonal antibodies to PD1 and PDL1 are currently being investigated in clinical trials for their potential to inhibit this pathway with the effect of elevated tumor immunity. Moreover, antibodies directed to PD-1 are also used for diagnosing certain T-cell derived lymphomas (for details see section reactivity).

Reactivity

Mouse monoclonal anti-PD-1 antibody clone NAT105 is suitable for the immunohistological detection of:

• Follicular helper T cells (TFH)
• Tumor-infitrating T cells (TILs) whose anti-tumor activity is inhibited by PD-1
• Lymphomas derived from TFH cells including:
  1. Angioimmunoblastic T-cell lymphoma
  2. Primary cutaneous CD4-positive small/medium T-cell lymphoma
  3. Follicular variant of peripheral T-cell lymphoma NOS

Immunostaining of formalin-fixed paraffin-embedded tissue sections for PD-1, clone NAT105, dilution 1:100

A: Lymph node. Note the strong labeling of the follicular T cells within the light zone of the germinal center.
B: Angioimmunoblastic T-cell lymphoma. The neoplastic cells are selectively labeled.
C: Primary cutaneous CD4-positive small/medium T-cell lymphoma. Insert shows labeled cells at a higher magnification.
D: Lymphocyte predominant Hodgkin lymphoma. The non-neoplastic T-cells expressing PD-1 form rosettes around the neoplastic LP cells.

A

B

C

D

(pictures courtesy of Prof. Dr. med. Harald Stein, Pathodiagnostik Berlin, Berlin, Germany)

Western blot analysis

Immunoblot of human YT cell line extracts using anti-PD-1 mouse monoclonal antibody clone NAT105 (DIA-PD1).

References to clone NAT105

1. Sato F, Ishida T, Ito A, Mori F, Masaki A, Takino H, Narita T, Ri M, Kusumoto S, Suzuki S, Komatsu H, Niimi A, Ueda R, Inagaki H, Iida S. Angioimmunoblastic T-cell lymphoma mice model. Leuk Res. 37(1): 21-27, 2013
2. Wahlin B E et al. Entourage: the immune microenvironment following follicular lymphoma Blood Cancer J 2:e52 (2012)
3. French JD et al. Programmed death-1+ T cells and regulatory T cells are enriched in tumor-involved lymph nodes and as-sociated with aggressive features in papillary thyroid cancer. J Clin Endocrinol Metab 97:E934-43 (2012).
4. Miyoshi H et al. Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioim-munoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders. Am J Clin Pathol 137:879-89 (2012).
5. Bruneau J et al. Regulatory T-cell depletion in angioimmunoblastic T-cell lymphoma. Am J Pathol 177:570-4 (2010)
6. Wada N et al. Diffuse large B-cell lymphoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lym-phoma): a study of Osaka Lymphoma Study Group. Virchows Arch 455:285-93 (2009)
7. Rodríguez-Pinilla SM, Roncador G, Rodríguez-Peralto JL, Mollejo M, García JF, Montes-Moreno S, Camacho FI, Ortiz P, Limeres-González MA, Torres A, Campo E, Navarro-Conde P, Piris MA. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma expresses follicular T-cell markers. Am J Surg Pathol. 2009 Jan;33(1):81-90.
8. Rodríguez-Pinilla SM, Atienza L, Murillo C, Pérez-Rodríguez A, Montes-Moreno S, Roncador G, Pérez-Seoane C, Domínguez P, Camacho FI, Piris MA. Peripheral T-cell lymphoma with follicular T-cell markers. Am J Surg Pathol. 2008. Dec;32(12):1787-99.
9. Nam-Cha SH, Roncador G, Sanchez-Verde L, Montes-Moreno S, Acevedo A, Domínguez-Franjo P, Piris MA. PD-1, a fol-licular Tcell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol. 2008 Aug;32(8):1252-7
10. Roncador, G., Verdes-Montenegro, J.F.G., Tedoldi, S., Paterson, J.C., Klapper, W., Ballabio, E., Maestre, L., Pileri, S., Hansmann, M.L., Piris, M.A., Mason, D.Y., Marafioti, T. Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma. Haematologica. 2007 Aug;92(8):1059-66.
11. Kang MJ, Kim KM, Bae JS, Park HS, Lee H, Chung MJ, Moon WS, Lee DG, Jang KY. Tumor-infiltrating PD1-Positive Lym-phocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma. Transl Oncol. 2013 Jun 1;6(3):282-9

Related References

1. Brusa D, Serra S, Coscia M, Rossi D, D’Arena G, Laurenti L, Jaksic O, Fedele G, Inghirami G, Gaidano G, Malavasi F, Deaglio S. The PD-1/PD-L1 axis contributes to T cell dysfunction in chronic lymphocytic leukemia. Haematologica [Epub ahead of print], Jan 8, 2013
2. Myklebust JH, Irish JM, Brody J, Czerwinski DK, Houot R, Kohrt HE, Timmerman J, Said J, Green MR, Delabie J, Kolstad A, Alizadeh AA, Levy R. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood [Epub ahead of print], Jan 7, 2013
3. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in pa-tients with advanced cancer. N Engl J Med. 2012;366:2455–65.
4. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24:207–12.
5. Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy: inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 18(24):6580-6587, 2012
6. Terme M, Ullrich E, Aymeric L, Meinhardt K, Desbois M, Delahaye N, et al. IL-18 induces PD-1-dependent immunosup-pression in cancer. Cancer Res. 2011;71:5393–9.
7. Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, et al. Tumor cell expression of programmed cell death-1 lig-and 1 is a prognostic factor for malignant melanoma. Cancer. 2010
8. Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol. 2010;11:535–42.
9. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009

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