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ABO血型与前列腺癌疫苗治疗的生存率相关。

ABO blood type correlates with survival on prostate cancer vaccine therapy.

作者信息

Muthana Saddam M, Gulley James L, Hodge James W, Schlom Jeffrey, Gildersleeve Jeffrey C

机构信息

Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Chemistry Department, College of Science & General Studies, Alfaisal University, Riyadh, KSA.

出版信息

Oncotarget. 2015 Oct 13;6(31):32244-56. doi: 10.18632/oncotarget.4993.

Abstract

Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging. Previously, we found that pre-treatment serum IgM to blood group A (BG-A) correlated with survival for patients treated with PROSTVAC-VF, a therapeutic cancer vaccine in phase III clinical trials for the treatment of prostate cancer. These results suggested that ABO blood type might influence efficacy. Unfortunately, blood types were not available in the clinical records for all but 8 patients and insufficient amounts of sera were left for standard blood typing methods. To test the hypothesis, therefore, we developed a new glycan microarray-based method for determining ABO blood type. The method requires only 4 μL of serum, provides 97% accuracy, and allows simultaneous profiling of many other serum anti-glycan antibodies. After validation with 220 healthy subjects of known blood type, the method was then applied to 74 PROSTVAC-VF patients and 37 control patients from a phase II trial. In this retrospective study, we found that type B and O PROSTVAC-VF patients demonstrated markedly improved clinical outcomes relative to A and AB patients, including longer median survival, longer median survival relative to Halabi predicted survival, and improved overall survival via Kaplan-Meier survival analysis (p = 0.006). Consequently, blood type may provide an inexpensive screen to pre-select patients likely to benefit from PROSTVAC-VF therapy.

摘要

癌症免疫疗法正在改变患者护理方式,但患者的临床反应差异很大。采用简单、廉价的策略将治疗靶向可能的反应者,可以显著提高疗效,同时降低医疗成本,但事实证明,识别可靠的生物标志物具有挑战性。此前,我们发现,治疗前血清中针对A血型(BG-A)的IgM与接受PROSTVAC-VF治疗的患者的生存率相关,PROSTVAC-VF是一种用于治疗前列腺癌的III期临床试验中的治疗性癌症疫苗。这些结果表明ABO血型可能会影响疗效。不幸的是,除了8名患者外,所有患者的临床记录中都没有血型信息,而且剩余的血清量不足以进行标准血型检测。因此,为了验证这一假设,我们开发了一种基于聚糖微阵列的新方法来确定ABO血型。该方法仅需4μL血清,准确率达97%,并能同时对许多其他血清抗聚糖抗体进行分析。在用220名已知血型的健康受试者进行验证后,该方法随后应用于一项II期试验的74名PROSTVAC-VF患者和37名对照患者。在这项回顾性研究中,我们发现,与A型和AB型患者相比,B型和O型PROSTVAC-VF患者的临床结果有显著改善,包括更长的中位生存期、相对于哈拉比预测生存期更长的中位生存期,以及通过Kaplan-Meier生存分析得出的更好的总生存期(p = 0.006)。因此,血型可能提供一种廉价的筛查方法,用于预先选择可能从PROSTVAC-VF治疗中受益的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c35/4741674/f5862fd17828/oncotarget-06-32244-g001.jpg

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