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人自然杀伤(NK)细胞表达的针对CD33和CD16(FcγRIII)的双特异性抗体对白血病细胞裂解的增强作用。

Potentiation of lysis of leukaemia cells by a bispecific antibody to CD33 and CD16 (Fc gamma RIII) expressed by human natural killer (NK) cells.

作者信息

Silla L M, Chen J, Zhong R K, Whiteside T L, Ball E D

机构信息

Division of Hematology/Bone Marrow Transplantation, University of Pittsburgh School of Medicine, Pennsylvania, USA.

出版信息

Br J Haematol. 1995 Apr;89(4):712-8. doi: 10.1111/j.1365-2141.1995.tb08406.x.

DOI:10.1111/j.1365-2141.1995.tb08406.x
PMID:7772507
Abstract

Bispecific antibodies recognizing tumour-associated antigens and trigger molecules expressed on immune effector cells have been shown to redirect cytotoxicity of several types of peripheral blood cells against relevant tumour targets. Among various effector cells, natural killer (NK) cells appear to play a role in defence against leukaemia. Here we report the successful chemical conjugation of monoclonal antibodies to CD33 and CD16 to create a bispecific antibody (BsAb 251 x 3G8). This bispecific antibody is capable of augmenting the killing of otherwise resistant leukaemia cells by peripheral blood lymphocytes (PBL), purified resting NK (R-NK) cells, and activated NK (A-NK) cells. BsAb 251 x 3G8 may play a role in the therapy of acute myeloid leukaemia (AML) through redirecting the cytotoxic activity of endogenous or adoptively transferred NK cells.

摘要

识别肿瘤相关抗原和免疫效应细胞上表达的触发分子的双特异性抗体已被证明可将几种外周血细胞的细胞毒性重定向至相关肿瘤靶标。在各种效应细胞中,自然杀伤(NK)细胞似乎在抵御白血病中发挥作用。在此,我们报告了将单克隆抗体与CD33和CD16成功进行化学偶联以产生双特异性抗体(BsAb 251 x 3G8)。这种双特异性抗体能够增强外周血淋巴细胞(PBL)、纯化的静息NK(R-NK)细胞和活化的NK(A-NK)细胞对原本耐药的白血病细胞的杀伤作用。BsAb 251 x 3G8可能通过重定向内源性或过继转移的NK细胞的细胞毒性活性在急性髓系白血病(AML)治疗中发挥作用。

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