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Identification of a Novel P190-Derived Breakpoint Peptide Suitable for Peptide Vaccine Therapeutic Approach in Ph+ Acute Lymphoblastic Leukemia Patients

机译:新型P190衍生断点肽的鉴定,适用于Ph +急性淋巴细胞白血病患者中的肽疫苗治疗方法

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Ph+ acute lymphoblastic leukemia (Ph+ ALL) is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22)(q34;q11) translocation results in a chimeric bcr-abl (e1a2 breakpoint) and in a 190 KD protein (p190) with constitutive tyrosine kinase activity. The advent of first- and second-generation tyrosine kinase inhibitors (TKIs) improved the short-term outcome of Ph+ ALL patients not eligible for allo-SCT; yet disease recurrence is almost inevitable. Peptides derived from p190-breakpoint area are leukemia-specific antigens that may mediate an antitumor response toward p190+ leukemia cells. We identified one peptide named p190-13 able to induce in vitro peptide-specific CD4+ T cell proliferation in Ph+ ALL patients in complete remission during TKIs. Thus this peptide appears a good candidate for developing an immune target vaccine strategy possibly synergizing with TKIs for remission maintenance.
机译:Ph +急性淋巴细胞白血病(Ph + ALL)是一种预后不良的高危急性白血病,其中特定的t(9; 22)(q34; q11)易位导致嵌合bcr-abl(e1a2断裂点)和190具有组成型酪氨酸激酶活性的KD蛋白(p190)。第一代和第二代酪氨酸激酶抑制剂(TKIs)的出现改善了不符合allo-SCT的Ph + ALL患者的短期预后。然而疾病的复发几乎是不可避免的。源自p190断裂点区域的肽是白血病特异性抗原,可介导针对p190 +白血​​病细胞的抗肿瘤反应。我们确定了一种名为p190-13的肽,能够在TKI期间完全缓解的Ph + ALL患者中诱导体外肽特异性CD4 + T细胞增殖。因此,该肽似乎是开发免疫靶疫苗策略的良好候选者,该策略可能与TKI协同作用以维持缓解。

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