Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies.
Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies.
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发表时间：
1989-09
期刊：
影响因子：
11.2
通讯作者：
O. Press;A. Farr;Borroz Ki;S. Anderson;P. Martin
中科院分区：
文献类型：
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作者：
O. Press;A. Farr;Borroz Ki;S. Anderson;P. Martin
在临床前研究中，分析了7种识别B淋巴细胞分化抗原的小鼠单抗(MoAbs)，以期用于B细胞恶性肿瘤的抗体靶向治疗。研究了HD37(抗CD19)、1F5(抗CD20)、HD6(抗CD22)、MB-1(抗CD37)、G28-5(抗CDw40)、7.2(抗II类)和DA4-4(抗IgM)的结合亲和力、免疫反应性、同型、内吞速率、降解率和Daudi细胞上的结合位点数。Lineweaver-Burke分析显示，125I标记的MoAbs的免疫反应性在59%到92%之间。125I-MoAbScatchard分析表明，其中5个抗体的结合亲和力大于10(9)L/M，而MoAb1F5和HD37的亲和力为3-4×10(8)L/M，CD20、CD37、Mu和HLAII类在Daudi细胞上高表达(200,000-400,000个结合位点/细胞)，而CD19、CD22和CDw40表达较少(80,000-100,000个结合位点/细胞)。DA4-4(MU)、HD6(CD22)和G28-5(CDw40)被细胞快速内化，HD37(CD19)和MB-1(CD37)中速内吞，7.2(II类)和1F5(CD20)内化缓慢。三氯乙酸沉淀和高效液相色谱分析表明，125I-Moab的相对降解率为：DA4-4>HD6(CD22)>HD37(CD19)>G28-5(CDw40)>MB-1(CD37)>1F5(CD20)>7.2(II类)。
Seven murine monoclonal antibodies (MoAbs) recognizing differentiation antigens present on B-lymphocytes were analyzed in preclinical studies for their potential use for antibody-targeted therapy of B-cell malignancies. MoAbs HD37 (anti-CD19), 1F5 (anti-CD20), HD6 (anti-CD22), MB-1 (anti-CD37), G28-5 (anti-CDw40), 7.2 (anti-class II), and DA4-4 (anti-IgM) were studied for their binding avidities, immunoreactivities, isotypes, endocytosis rates, degradation rates, and number of binding sites on Daudi cells. Lineweaver-Burke analyses of 125I-labeled MoAbs demonstrated immunoreactivities ranging from 59 to 92%. Scatchard analyses of 125I-MoAbs demonstrated that five of the antibodies had binding avidities in excess of 10(9) L/M, whereas MoAbs 1F5 and HD37 had avidities of 3-4 x 10(8) L/M. CD20, CD37, mu, and HLA Class II were found to be highly expressed (200,000-400,000 binding sites/cell) on Daudi cells whereas CD19, CD22, and CDw40 were less densely expressed (80,000-100,000 sites/cell). DA4-4 (mu), HD6 (CD22), and G28-5 (CDw40) were rapidly internalized by cells, HD37 (CD19) and MB-1 (CD37) underwent endocytosis at an intermediate rate, and 7.2 (class II) and 1F5 (CD20) were internalized slowly. Trichloroacetic acid precipitation and high-performance liquid chromatography revealed the following relative rates of 125I-MoAb degradation: DA4-4 (mu) greater than HD6 (CD22) greater than HD37 (CD19) greater than G28-5 (CDw40) greater than MB-1 (CD37) greater than 1F5 (CD20) greater than 7.2 (class II).