Sự biểu hiện quá mức liên tục của một protein mới 21 kDa ở Lymphoma Hodgkin và Lymphoma không Hodgkin ác tính

Molecular Cancer - Tập 7 - Trang 1-11 - 2008
Minglong Zhou1, Faisal M Fadlelmola1, Jason B Cohn2, Brian Skinnider1,3, Randy D Gascoyne1,3, Diponkar Banerjee1,3
1Centre for Translational and Applied Genomics (CTAG), Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver Cancer Centre, Canada
2Samuel Lunenfeld Research Institute, Toronto, Canada
3University of British Columbia, Vancouver, Canada

Tóm tắt

CD30, một protein bề mặt phosphoryl hoá nặng 120 kDa, là một thành viên của gia đình thụ thể hoại tử khối u/yếu tố tăng trưởng thần kinh (TNF/NGFR) và được biểu hiện liên tục bởi các tế bào Hodgkin và Reed-Sternberg (HRS) trong lymphoma Hodgkin (HL) cùng với các tế bào ác tính của Lymphoma Tế bào lớn ác tính (ALCL). Một dấu hiệu protein đặc hiệu cho bệnh vẫn chưa được xác định trong các tế bào của lymphoma Hodgkin. Để xác định các dấu ấn sinh học đặc hiệu cho HL, các kháng thể đơn dòng murine mới đã được phát triển trong phòng thí nghiệm của chúng tôi. Các kháng thể đơn dòng murine (mabs) được tạo ra nhằm chống lại nhánh con B3 của dòng tế bào KM-H2 nguồn gốc từ HL. Hai trong số các mabs này (mab clone R23.1 và mab clone R24.1) là kháng thể loại IgG1 nhận diện một protein nặng 21 kDa có mặt tại màng tế bào và trong bào tương của các dòng tế bào nguồn gốc từ HL. Mab clone R24.1 nhận diện một epitope kháng formalin và đánh dấu các tế bào HRS trong các mẫu mô từ những bệnh nhân bị HL dạng cổ điển, ALCL, và các kiểu con của lymphoma không Hodgkin ác tính tế bào T và B. Phân tử kháng nguyên được nhận diện bởi mab clone R23.1 và mab clone R24.1 không chia sẻ các epitope với các vùng cụm CD30 A, B, hay C, và, không giống như CD30, không được biểu hiện bởi các tế bào T được kích hoạt bởi phytohemagglutinin (PHA). Protein 21 kDa được phát hiện bởi các mab clone R23.1 và clone R24.1 là một protein liên kết màng mới, có thể là một dấu hiệu tiềm năng cho chẩn đoán và liệu pháp nhắm mục tiêu đối với HL cùng với lymphoma không Hodgkin ác tính tế bào T và B.

Từ khóa

#Lymphoma Hodgkin #protein 21 kDa #kháng thể đơn dòng #kháng nguyên #điều trị nhắm mục tiêu

Tài liệu tham khảo

Schwarting R, Gerdes J, Durkop H, Falini B, Pileri S, Stein H: BER-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood. 1989, 74: 1678-1689. Durkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H: Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell. 1992, 68: 421-427. Horn-Lohrens O, Tiemann M, Lange H, Kobarg J, Hafner M, Hansen H, Sterry W, Parwaresch RM, Lemke H: Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4). Int J Cancer. 1995, 60: 539-544. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, Schwarting R, Lennert k: The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985, 66: 848-858. Delsol G, Al Saati T, Gatter KC, Gerdes J, Schwarting R, Caveriviere P, Rigal-Huguet F, Robert A, Stein H, Mason DY: Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis. Am J Pathol. 1988, 130: 59-70. Higgins JP, Warnke RA: CD30 expression is common in mediastinal large B-cell lymphoma. American journal of clinical pathology. 1999, 112: 241-247. Piris M, Brown DC, Gatter KC, Mason DY: CD30 expression in non-Hodgkin's lymphoma. Histopathology. 1990, 17: 211-218. Miettinen M: CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin's and non-Hodgkin's lymphomas. Archives of pathology & laboratory medicine. 1992, 116: 1197-1201. Latza U, Foss HD, Durkop H, Eitelbach F, Dieckmann KP, Loy V, Unger M, Pizzolo G, Stein H: CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. Am J Pathol. 1995, 146: 463-471. Hansen H, Lemke H, Bredfeldt G, Konnecke I, Havsteen B: The Hodgkin-associated Ki-1 antigen exists in an intracellular and a membrane-bound form. Biological chemistry Hoppe-Seyler. 1989, 370: 409-416. Paloczi K, Pocsik E, Kotlan B, Ujhelyi E, Timar L, Petranyi GG: The pattern of activation antigen expression on T-lymphocyte subpopulation in infectious mononucleosis. Haematologia. 1991, 24: 83-90. Bashir MS, Jones DB, Wright DH: Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells. Clinical and Experimental Immunology. 1992, 88: 543-547. Ellis TM, Simms PE, Slivnick DJ, Jack HM, Fisher RI: CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. Journal of Immunology (Baltimore, Md). 1993, 151: 2380-2389. Vinante F, Morosato L, Siviero F, Nadali G, Rigo A, Veneri D, deSabata D, Vincenzi C, Chilosi M, Semenzato G: Soluble forms of p55-IL-2R alpha, CD8, and CD30 molecules as markers of lymphoid cell activation in infectious mononucleosis. Haematologica. 1994, 79: 413-419. Piletta PA, Wirth S, Hommel L, Saurat JH, Hauser C: Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B phototherapy. Archives of dermatology. 1996, 132: 1171-1176. Chittal SM, Caveriviere P, Schwarting R, Gerdes J, Al Saati T, Rigal-Huguet F, Stein H, Delsol G: Monoclonal antibodies in the diagnosis of Hodgkin's disease. The search for a rational panel. The American journal of surgical pathology. 1988, 12: 9-21. Casey TT, Olson SJ, Cousar JB, Collins RD: Immunophenotypes of Reed-Sternberg cells: a study of 19 cases of Hodgkin's disease in plastic-embedded sections. Blood. 1989, 74: 2624-2628. Agnarsson BA, Kadin ME: The immunophenotype of Reed-Sternberg cells. A study of 50 cases of Hodgkin's disease using fixed frozen tissues. Cancer. 1989, 63: 2083-2087. Amin HM, Lai R: Pathobiology of ALK+ anaplastic large-cell lymphoma. Blood. 2007, 110: 2259-2267. Falini B, Venturi S, Martelli M, Santucci A, Pileri S, Pescarmona E, Giovannini M, Mazza P, Martelli MF, Pasqualucci L, Ballatori E, Guglielmi C, Amadori S, Poggi S, Sabattini E, Gherlinzoni F, Zinzani PL, Baroni CD, Mandelli F, Tura S: Mediastinal large B-cell lymphoma: clinical and immunohistological findings in 18 patients treated with different third-generation regimens. British journal of haematology. 1995, 89: 780-789. Maes B, Anastasopoulou A, Kluin-Nelemans JC, Teodorovic I, Achten R, Carbone A, De Wolf-Peeters C: Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+ anaplastic B-cell subtypes exhibit distinct clinical features. Annals of oncology. 2001, 12: 853-858. Martinez AE, Lin L, Dunphy CH: Grading of follicular lymphoma: comparison of routine histology with immunohistochemistry. Archives of pathology & laboratory medicine. 2007, 131: 1084-1088. Lazaris AC, Nonni A, Pathiaki I, Patsouris E: Primary diffuse large B-cell lymphoma of the skin. Dermatology online journal. 2006, 12: 16- Magro CM, Nash JW, Werling RW, Porcu P, Crowson N: Primary cutaneous CD30+ large cell B-cell lymphoma: a series of 10 cases. Applied immunohistochemistry & molecular morphology. 2006, 14: 7-11. 10.1097/01.pai.0000143347.58174.91. Garcia JF, Mollejo M, Fraga M, Forteza J, Muniesa JA, Perez-Guillermo M, Perez-Seoane C, Rivera T, Ortega P, Piris MA: Large B-cell lymphoma with Hodgkin's features. Histopathology. 2005, 47: 101-110. Tao K, Zhu X, Xu W, Chen Z, Lu H: A clinicopathologic and immunohistochemical study of diffuse large B-cell lymphoma. Zhonghua bing li xue za zhi Chinese journal of pathology. 2002, 31: 112-115. Dominis M, Dzebro S, Gasparov S, Pesut A, Kusec R: Diffuse large B-cell lymphoma and its variants. Croatian medical journal. 2002, 43: 535-540. Herrera E, Gallardo M, Bosch R, Cabra B, Aneri V, Sanchez P: Primary cutaneous CD30 (Ki-1)-positive non-anaplastic B-cell lymphoma. Journal of cutaneous pathology. 2002, 29: 181-184. Dargent JL, Lespagnard L, Sirtaine N, Cantinieaux B, Li R, Hermans P: Plasmablastic microlymphoma occurring in human herpesvirus 8 (HHV-8)-positive multicentric Castleman's disease and featuring a follicular growth pattern. APMIS. 2007, 115: 869-874. Gorczyca W, Tsang P, Liu Z, Wu CD, Dong HY, Goldstein M, Cohen P, Gangi M, Weisberger J: CD30-positive T-cell lymphomas co-expressing CD15: an immunohistochemical analysis. International journal of oncology. 2003, 22: 319-324. Wada K, Maesawa C, Satoh T, Akasaka T, Masuda T: A case of primary cutaneous CD30+ T-cell lymphoproliferative disorder with features of granulomatous slack skin disease. The British journal of dermatology. 2002, 147: 998-1002. Au WY, Yeung CK, Chan HH, Wong RW, Shek TW: CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour. The British journal of dermatology. 2002, 146: 1091-1095. Pallesen G, Hamilton-Dutoit SJ: Ki-1 (CD30) antigen is regularly expressed by tumor cells of embryonal carcinoma. The American journal of pathology. 1988, 133: 446-450. Ferreiro JA: Ber-H2 expression in testicular germ cell tumors. Human pathology. 1994, 25: 522-524. Latza U, Foss HD, Durkop H, Eitelbach F, Dieckmann KP, Loy V, Unger M, Pizzolo G, Stein H: CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. The American journal of pathology. 1995, 146: 463-471. Durkop H, Foss HD, Eitelbach F, Anagnostopoulos I, Latza U, Pileri S, Stein H: Expression of the CD30 antigen in non-lymphoid tissues and cells. The Journal of pathology. 2000, 190: 613-618. Tamiolakis D, Papadoupoulos N, Venizelos I, Lambropoulou M, Tsikouras P, Koutsougeras G, Bolioti S, Tsiapali M, Karpouzis A, Kouskoukis C: CD30 (Ki-1) molecule expression in human embryonal epithelial cells of the basal layer of the developing epidermis and epidermal buds and its potential significance for embryogenesis. Acta dermatovenerologica Alpina, Panonica, et Adriatica. 2005, 14: 85-90. 92 Bolognesi A, Tazzari PL, Legname G, Olivieri F, Modena D, Conte R, Stirpe F: Anti-CD30 immunotoxins with native and recombinant dianthin 30. Cancer Immunol Immunother. 1995, 40: 109-114. Klimka A, Barth S, Matthey B, Roovers RC, Lemke H, Hansen H, Arends JW, Diehl V, Hoogenboom HR, Engert A: An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETA') is a potent immunotoxin against a Hodgkin-derived cell line. Br J Cancer. 1999, 80: 1214-1222. Schlapschy M, Gruber H, Gresch O, Schafer C, Renner C, Pfreundschuh M, Skerra A: Functional humanization of an anti-CD30 Fab fragment for the immunotherapy of Hodgkin's lymphoma using an in vitro evolution approach. Protein Eng Des Sel. 2004, 17: 847-860. Borchmann P, Schnell R, Schulz H, Engert A: Monoclonal antibody-based immunotherapy of Hodgkin's lymphoma. Curr Opin Investig Drugs. 2004, 5: 1262-1267. Heuser C, Guhlke S, Matthies A, Bender H, Barth S, Diehl V, Abken H, Hombach A: Anti-CD30-scFv-Fc-IL-2 antibody-cytokine fusion protein that induces resting NK cells to highly efficient cytolysis of Hodgkin's lymphoma derived tumour cells. Int J Cancer. 2004, 110: 386-394. Borchmann P, Treml JF, Hansen H, Gottstein C, Schnell R, Staak O, Zhang HF, Davis T, Keler T, Diehl V, Graziano RF, Engert A: The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma. Blood. 2003, 102: 3737-3742. Borchmann P, Schnell R, Fuss I, Manzke O, Davis T, Lewis LD, Behnke D, Wickenhauser C, Schiller P, Diehl V, Engert A: Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma. Blood. 2002, 100: 3101-3107. Renner C, Stehle I, Lee FT, Hall C, Catimel B, Nice EC, Mountain A, Rigopoulos A, Brechbiel MW, Pfreundschuh M, Scott AM: Targeting properties of an anti-CD16/anti-CD30 bispecific antibody in an in vivo system. Cancer Immunol Immunother. 2001, 50: 102-108. Matthey B, Engert A, Barth S: Recombinant immunotoxins for the treatment of Hodgkin's disease (Review). Int J Mol Med. 2000, 6: 509-514. Barth S, Huhn M, Matthey B, Tawadros S, Schnell R, Schinkothe T, Diehl V, Engert A: Ki-4(scFv)-ETA', a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice. Blood. 2000, 95: 3909-3914. Tian ZG, Longo DL, Funakoshi S, Asai O, Ferris DK, Widmer M, Murphy WJ: In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large-cell lymphoma xenografts. Cancer Res. 1995, 55: 5335-5341. Falini B, Bolognesi A, Flenghi L, Tazzari PL, Broe MK, Stein H, Durkop H, Aversa F, Corneli P, Pizzolo G, Barbabietola G, Sabattini E, Pileri S, Martelli MF, Stirpe F: Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin. Lancet. 1992, 339: 1195-1196. Schnell R, Dietlein M, Staak JO, Borchmann P, Schomaecker K, Fischer T, Eschner W, Hansen H, Morschhauser F, Schicha H, Diehl V, Raubitschek A, Engert A: Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol. 2005, 23: 4669-4678. Koon HB, Junghans RP: Anti-CD30 antibody-based therapy. Curr Opin Oncol. 2000, 12: 588-593. Arenaz P, Sirover MA: Isolation and characterization of monoclonal antibodies directed against the DNA repair enzyme uracil DNA glycosylase from human placenta. Proc Natl Acad Sci USA. 1983, 80: 5822-5826. Ramshaw HS, Haylock D, Swart B, Gronthos S, Horsfall MJ, Niutta S, Simmons PJ: Monoclonal antibody BB9 raised against bone marrow stromal cells identifies a cell-surface glycoprotein expressed by primitive human hemopoietic progenitors. Exp Hematol. 2001, 29: 981-992. Sambrook J, Fritsch E, Maniatis T: Molecular Cloning: A Laboratory Manual. 1989, Cold Spring Harbor Laboratory, New York