CD99被证明是T急性淋巴细胞白血病(T-ALL)抗体治疗的潜在靶标。通过某些单克隆抗体(mAb)连接CD99诱导T-ALL凋亡。然而,在抗CD99mAb参与后导致T-ALL凋亡的分子基础仍然难以捉摸。在这项研究中,使用我们产生的抗CD99单克隆抗体克隆MT99/3(单克隆抗体MT99/3),mAbMT99/3接合强烈诱导T-ALL细胞系凋亡,但不是在非恶性外周血细胞。通过转录组分析,在mAbMT99/3结扎,13个凋亡相关基因,包括FOS,TNF,FASLG,BCL2A1,JUNB,SOCS1,IL27RA,PTPN6,PDGFA,NR4A1,SGK1,LPAR5和LTB,显着上调。然后,由mAbMT99/3识别的CD99的表位在CD99的残基60-70处被鉴定为VDGENDDPRPP,这从未被报道过。据我们所知,这是在T-ALL中使用抗CD99mAb进行的第一个转录组数据。这些发现为CD99与T-ALL的凋亡有关提供了新的见解。与mAbMT99/3诱导凋亡相关的新表位和凋亡相关基因的鉴定可以作为T-ALL的新治疗靶标。抗CD99mAb克隆MT99/3可能是进一步开发用于T-ALL疗法的治疗性抗体的候选者。
CD99 was demonstrated to be a potential target for antibody therapy on T-acute lymphoblastic leukemia (T-ALL). The ligation of CD99 by certain monoclonal antibodies (mAbs) induced T-ALL apoptosis. However, the molecular basis contributing to the apoptosis of T-ALL upon anti-CD99 mAb engagement remains elusive. In this study, using our generated anti-CD99 mAb clone MT99/3 (mAb MT99/3), mAb MT99/3 engagement strongly induced apoptosis of T-ALL cell lines, but not in non-malignant peripheral blood cells. By transcriptome analysis, upon mAb MT99/3 ligation, 13 apoptosis-related genes, including FOS, TNF, FASLG, BCL2A1, JUNB, SOCS1, IL27RA, PTPN6, PDGFA, NR4A1, SGK1, LPAR5 and LTB, were significantly upregulated. The epitope of CD99 recognized by mAb MT99/3 was then identified as the VDGENDDPRPP at residues 60-70 of CD99, which has never been reported. To the best of our knowledge, this is the first transcriptome data conducted in T-ALL with anti-CD99 mAb engagement. These findings provide new insights into CD99 implicated in the apoptosis of T-ALL. The identification of a new epitope and apoptosis-related genes that relate to the induction of apoptosis by mAb MT99/3 may serve as a new therapeutic target for T-ALL. The anti-CD99 mAb clone MT99/3 might be a candidate for further development of a therapeutic antibody for T-ALL therapy.