Li Fenge, Wu Huancheng, Du Xueming, Sun Yimo, Rausseo Barbara Nassif, Talukder Amjad, Katailiha Arjun, Elzohary Lama, Wang Yupeng, Wang Zhiyu, Lizée Gregory
Core Laboratory, Tianjin Beichen Hospital, Tianjin 300400, China.
Department of Oncology, Tianjin Beichen Hospital, Tianjin 300400, China.
Vaccines (Basel). 2023 Sep 5;11(9):1460. doi: 10.3390/vaccines11091460.
The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide vaccines targeting mutated EGFR have been tested in multiple clinical trials, demonstrating an excellent safety profile and encouraging clinical efficacy. For example, the CDX-110 (rindopepimut) NeoAg peptide vaccine derived from the EGFRvIII deletion mutant in combination with temozolomide and radiotherapy has shown efficacy in treating EGFRvIII-harboring glioblastoma multiforme (GBM) patients undergone surgery in multiple Phase I and II clinical trials. Furthermore, pilot clinical trials that have administered personalized NeoAg peptides for treating advanced-stage NSCLC patients have shown this approach to be a feasible and safe method to increase antitumor immune responses. Amongst the vaccine peptides administered, EGFR mutation-targeting NeoAgs induced the strongest T cell-mediated immune responses in patients and were also associated with objective clinical responses, implying a promising future for NeoAg peptide vaccines for treating NSCLC patients with selected EGFR mutations. The efficacy of NeoAg-targeting peptide vaccines may be further improved by combining with other modalities such as tyrosine kinase or immune checkpoint inhibitor (ICI) therapy, which are currently being tested in animal models and clinical trials. Herein, we review the most current basic and clinical research progress on EGFR-targeted peptide vaccination for the treatment of NSCLC and other solid tumor types.
表皮生长因子受体（EGFR）在多种重要生物学功能中发挥关键作用，如胚胎发生、上皮组织发育和细胞再生。然而，在多种实体瘤类型中，该基因的过表达和/或激活突变经常发生，从而劫持EGFR信号通路以促进肿瘤发生。特别是非小细胞肺癌（NSCLC）肿瘤通常含有普遍且共有的EGFR突变，这为公共新抗原（NeoAg）提供了理想来源。在人类和动物模型中的研究均证实了其中一些NeoAg肽的免疫原性，表明它们可能构成癌症免疫疗法的可行靶点。针对突变型EGFR的肽疫苗已在多项临床试验中进行了测试，显示出良好的安全性和令人鼓舞的临床疗效。例如，源自EGFRvIII缺失突变体的CDX-110（rindopepimut）NeoAg肽疫苗与替莫唑胺和放疗联合使用，在多个I期和II期临床试验中已显示出对接受手术的携带EGFRvIII的多形性胶质母细胞瘤（GBM）患者的治疗效果。此外，给予晚期NSCLC患者个性化NeoAg肽的试点临床试验表明，这种方法是增加抗肿瘤免疫反应的可行且安全的方法。在所给予的疫苗肽中，靶向EGFR突变的NeoAgs在患者中诱导了最强的T细胞介导的免疫反应，并且还与客观临床反应相关，这意味着针对具有特定EGFR突变的NSCLC患者的NeoAg肽疫苗前景广阔。通过与其他方式如酪氨酸激酶或免疫检查点抑制剂（ICI）疗法联合使用，靶向NeoAg的肽疫苗的疗效可能会进一步提高，目前正在动物模型和临床试验中对此进行测试。在此，我们综述了针对EGFR的肽疫苗治疗NSCLC和其他实体瘤类型的最新基础和临床研究进展。
