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黑色素瘤特异性抗原相关抗肿瘤抗体反应性作为靶向免疫治疗的免疫相关生物标志物

英文原题:Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies.

查看英文原题

Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies.

PubMed 2022/05/11(内容时间) Commun Med (Lond) Q1 · IF 7.4(JCR 2025)

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研究概要

本研究为靶向免疫治疗相关的肿瘤特异性免疫原性的差异和相似性提供了见解。抗体表位作为生物标志物反映了黑色素瘤相关的免疫应答特征,也为参与癌症发病机制的分子通路提供了见解。总之,抗体表位应答可用于预测免疫治疗所激发的抗癌免疫。

研究思路结论见上方概要

免疫疗法,包括癌症疫苗和免疫检查点抑制剂,已经改变了许多癌症的治疗方式。然而,大量患者对这些免疫疗法表现出耐药性,目前的研究在预测精准免疫治疗反应方面的发现有限。

在此,我们应用下一代噬菌体展示模拟表位变异分析(MVA)来描绘抗体反应,并剖析体液免疫在靶向癌症治疗中的作用,即抗肿瘤树突状细胞疫苗(MelCancerVac ®)和抗PD-1单克隆抗体(pembrolizumab)免疫治疗。

对抗体免疫应答的分析使得与黑色素瘤相关抗原和癌-睾丸抗原(CTA)相关的表位得以表征,这些表位在肺癌的MelCancerVac®治疗中诱导了抗体应答。其中若干表位与在接受抗PD-1治疗的不可切除转移性黑色素瘤患者中具有强免疫应答的抗原一致。

展开英文摘要原文

Immunotherapies, including cancer vaccines and immune checkpoint inhibitors have transformed the management of many cancers. However, a large number of patients show resistance to these immunotherapies and current research has provided limited findings for predicting response to precision immunotherapy treatments.

Here, we applied the next generation phage display mimotope variation analysis (MVA) to profile antibody response and dissect the role of humoral immunity in targeted cancer therapies, namely anti-tumor dendritic cell vaccine (MelCancerVac ® ) and immunotherapy with anti-PD-1 monoclonal antibodies (pembrolizumab).

Analysis of the antibody immune response led to the characterization of epitopes that were linked to melanoma-associated and cancer-testis antigens (CTA) whose antibody response was induced upon MelCancerVac® treatments of lung cancer. Several of these epitopes aligned to antigens with strong immune response in patients with unresectable metastatic melanoma receiving anti-PD-1 therapy.

This study provides insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments. The antibody epitopes as biomarkers reflect melanoma-associated features of immune response, and also provide insights into the molecular pathways contributing to the pathogenesis of cancer. Concluding, antibody epitope response can be useful in predicting anti-cancer immunity elicited by immunotherapy.

论文信息

作者
Rähni A、Jaago M、Sadam H、Pupina N、Pihlak A、Tuvikene J、Annuk M、Mägi A
单位
Protobios Llc, Tallinn, Estonia.Estonia
期刊
Communications medicine2022
原文标识
PubMed 35603273 · DOI 10.1038/s43856-022-00114-7