文章：

在对K562/GVAX免疫治疗有临床反应的CML患者中诱导针对多种白血病相关抗原的高滴度IgG抗体

Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy

原文发布日期：2013-09-06

DOI: 10.1038/bcj.2013.44

类型: Original Article

开放获取: 是

英文摘要：

The ability to target myeloid leukemia with immunotherapy would represent a significant therapeutic advance. We report here immunological analysis of clinical trials of primary and secondary vaccination with K562/GM-CSF immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP) with suboptimal responses to imatinib mesylate. Using serological analysis of recombinant cDNA expression libraries of K562 with autologous vaccinated patient serum, we have identified 12 novel chronic myeloid leukemia-associated antigens (LAAs). We show that clinical responses following K562/GM-CSF vaccination are associated with induction of high-titer antibody responses to multiple LAAs. We observe markedly discordant patterns of baseline and induced antibody responses in these identically vaccinated patients. No single antigen was recognized in all responses to vaccination. We demonstrate that an additional ‘booster’ vaccination series can be given safely to those with inadequate responses to initial vaccination, and is associated with more frequent induction of IgG responses to antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally, those with induced immune responses to the same LAAs often shared HLA subtypes and patients with clinical responses following vaccination recognized a partially shared but non-identical spectrum of antigens; both findings have potentially significant implications for cancer vaccine immunotherapy.

摘要翻译： 

利用免疫疗法靶向治疗髓系白血病将是一项重要的治疗进展。本文报告了对伊马替尼治疗效果不佳的成人慢性期慢性髓系白血病患者进行K562/GM-CSF免疫治疗初免与加强接种的临床试验免疫学分析。通过使用自体接种患者血清对K562重组cDNA表达文库进行血清学分析，我们鉴定出12种新型慢性髓系白血病相关抗原。研究发现K562/GM-CSF疫苗接种后的临床反应与针对多个白血病相关抗原的高滴度抗体反应诱导相关。我们在这些接受相同疫苗接种的患者中观察到基线抗体反应与诱导抗体反应存在显著差异模式。未发现单一抗原在所有疫苗接种反应中均被识别。研究证实，对初始疫苗接种反应不足的患者可安全接受额外"加强"接种系列，且与原发性慢性期慢性髓系白血病相比，该方案更频繁诱导针对K562疫苗中过表达抗原的IgG反应。最后，对相同白血病相关抗原产生诱导免疫应答的个体往往具有相同的HLA亚型，且疫苗接种后获得临床缓解的患者识别部分共通但非完全相同的抗原谱——这两项发现对癌症疫苗免疫治疗均具有潜在重要意义。

原文链接：

Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy