A fully human CD19/CD3 bi-specific antibody triggers potent and specific cytotoxicity by unstimulated T lymphocytes against non-Hodgkin's lymphoma

被引：3
作者：
Zhou, Yan [1 ]
Gou, Lan-tu [1 ]
Mu, Bo [1 ]
Liao, Wei-chan [1 ]
He, Jing [1 ]
Ma, Cong [1 ]
Yao, Yu-qin [1 ]
Yang, Jin-liang [1 ]
机构：
[1] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Chengdu 610041, Sichuan, Peoples R China
来源：
BIOTECHNOLOGY LETTERS | 2012年 / 34卷 / 07期
基金：
国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词：
Bi-specific antibody; CD19; CD3; Non-Hodgkin's lymphoma; SINGLE-CHAIN ANTIBODY; BISPECIFIC ANTIBODIES; MONOCLONAL-ANTIBODY; IMMUNODEFICIENT MICE; CELL LYMPHOMA; COSTIMULATION; APOPTOSIS; CONSTRUCT; CD3;
D O I：
10.1007/s10529-012-0895-6
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
The use of a bi-specific antibody (BsAb) is an attractive and specific approach to cancer therapy. We have constructed a fully human recombinant single chain Fv BsAb against CD19 and CD3 that was an effective treatment in an animal model of non-Hodgkin's lymphoma (NHL). The CD19/CD3 BsAb was expressed in CHO cells and purified by Ni-column chromatography. Flow cytometry revealed that the CD19/CD3 BsAb specifically bound to both CD19 and CD3-positive cells. In vitro, the CD19/CD3 BsAb could stimulate T cell proliferation and induce the lysis of cultured Raji cells in the presence of unstimulated T lymphocytes. In vivo, the CD19/CD3 BsAb efficiently inhibited tumour growth in SCID mice of NHL, and the survival time of the mice was significantly prolonged. Therefore, our CD19/CD3 BsAb is a useful tool that could be a suitable candidate for treatment of NHL.
引用
收藏
页码：1183 / 1191
页数：9
相关论文
共 15 条
  • [1] Tumor regression in cancer patients by very low doses of a T cell-engaging antibody
    Bargou, Ralf
    Leo, Eugen
    Zugmaier, Gerhard
    Klinger, Matthias
    Goebeler, Mariele
    Knop, Stefan
    Noppeney, Richard
    Viardot, Andreas
    Hess, Georg
    Schuler, Martin
    Einsele, Hermann
    Brandl, Christian
    Wolf, Andreas
    Kirchinger, Petra
    Klappers, Petra
    Schmidt, Margit
    Riethmueller, Gert
    Reinhardt, Carsten
    Baeuerle, Patrick A.
    Kufer, Peter
    [J]. SCIENCE, 2008, 321 (5891) : 974 - 977
  • [2] Bohlen H, 1997, CANCER RES, V57, P1704
  • [3] Immunotherapy of B-cell lymphoma with CD3x19 bispecific antibodies:: Costimulation via CD28 prevents "veto" apoptosis of antibody-targeted cytotoxic T cells
    Daniel, PT
    Kroidl, A
    Kopp, J
    Sturm, I
    Moldenhauer, G
    Dörken, B
    Pezzutto, A
    [J]. BLOOD, 1998, 92 (12) : 4750 - 4757
  • [4] The production and purification of the human T-cell receptors, the CD3εγ and CD3εδ heterodimers:: complex formation and crystallization with OKT3, a therapeutic monoclonal antibody
    Dunstone, MA
    Kjer-Nielsen, LB
    Kostenko, L
    Purcell, AW
    Brooks, AG
    Rossjohn, J
    McCluskey, J
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 : 1425 - 1428
  • [5] THE EFFICACY OF CD3 X CD19 BISPECIFIC MONOCLONAL-ANTIBODY (BSAB) IN A CLONOGENIC-ASSAY - THE EFFECT OF REPEATED ADDITION OF BSAB AND INTERLEUKIN-2
    HAAGEN, IA
    GEERARS, AJG
    DELAU, WBM
    BAST, BJEG
    DEGAST, C
    [J]. BLOOD, 1995, 85 (11) : 3208 - 3212
  • [6] Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis
    Janas, E
    Priest, R
    Wilde, JI
    White, JH
    Malhotra, R
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2005, 139 (03) : 439 - 446
  • [7] Kipriyanov SM, 1998, INT J CANCER, V77, P763, DOI 10.1002/(SICI)1097-0215(19980831)77:5<763::AID-IJC16>3.0.CO
  • [8] 2-2
  • [9] Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts
    Lang, P
    Barbin, K
    Feuchtinger, T
    Greil, J
    Peipp, M
    Zunino, SJ
    Pfeiffer, M
    Handgretinger, R
    Niethammer, D
    Fey, GH
    [J]. BLOOD, 2004, 103 (10) : 3982 - 3985
  • [10] A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes
    Löffler, A
    Kufer, P
    Lutterbüse, R
    Zettl, F
    Daniel, PT
    Schwenkenbecher, JM
    Riethmüller, G
    Dörken, B
    Bargou, RC
    [J]. BLOOD, 2000, 95 (06) : 2098 - 2103
12