Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
复制标题
建立一种治疗性抗PAN HLA级II单克隆抗体，该抗体直接通过大孔形成诱导淋巴瘤细胞死亡。
DOI：
10.1371/journal.pone.0150496
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hino O
中科院分区：
文献类型：
--
作者：
Matsuoka S;Ishii Y;Nakao A;Abe M;Ohtsuji N;Momose S;Jin H;Arase H;Sugimoto K;Nakauchi Y;Masutani H;Maeda M;Yagita H;Komatsu N;Hino O
为了研制一种新的治疗霍奇金淋巴瘤(HL)的单抗，我们用活的HL细胞株交替免疫BALB/c小鼠。杂交后，我们通过评估对未用于免疫的HL细胞系的直接细胞毒性来筛选杂交瘤克隆。我们开发了这一策略来建立mAb，以降低获得单个HL细胞系特异性克隆型mAb的风险。一种新建立的小鼠抗人单抗(4713)在HL细胞系、Burkitt淋巴瘤细胞系和晚期成人T细胞白血病细胞系中引发细胞骨架依赖、但补体和caspase不依赖的细胞死亡。静脉注射mAb4713可显著提高SCID荷瘤小鼠的存活率。经鉴定，单抗4713为鼠抗人Pan-HLAII类单抗。用该单抗在30min内可在靶淋巴瘤细胞表面形成大孔。这一发现表明，这种抗PAN的HLAII类单抗诱导的细胞死亡过程可能涉及到与溶细胞性的抗PAN MHC I类单抗刺激的死亡信号相同的死亡信号，该单抗也可以诱导大孔的形成。这项多方面的研究支持单抗4713对各种形式的淋巴瘤的治疗潜力。
To develop a new therapeutic monoclonal Antibody (mAb) for Hodgkin lymphoma (HL), we immunized a BALB/c mouse with live HL cell lines, alternating between two HL cell lines. After hybridization, we screened the hybridoma clones by assessing direct cytotoxicity against a HL cell line not used for immunization. We developed this strategy for establishing mAb to reduce the risk of obtaining clonotypic mAb specific for single HL cell line. A newly established mouse anti-human mAb (4713) triggered cytoskeleton-dependent, but complement- and caspase-independent, cell death in HL cell lines, Burkitt lymphoma cell lines, and advanced adult T-cell leukemia cell lines. Intravenous injection of mAb 4713 in tumor-bearing SCID mice improved survival significantly. mAb 4713 was revealed to be a mouse anti-human pan-HLA class II mAb. Treatment with this mAb induced the formation of large pores on the surface of target lymphoma cells within 30 min. This finding suggests that the cell death process induced by this anti-pan HLA-class II mAb may involve the same death signals stimulated by a cytolytic anti-pan MHC class I mAb that also induces large pore formation. This multifaceted study supports the therapeutic potential of mAb 4713 for various forms of lymphoma.