Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma

被引:14
作者
Li, Fenge [1 ,2 ]
Wu, Huancheng [3 ]
Du, Xueming [2 ]
Sun, Yimo [4 ]
Rausseo, Barbara Nassif [4 ]
Talukder, Amjad [4 ]
Katailiha, Arjun [4 ]
Elzohary, Lama [4 ]
Wang, Yupeng [2 ]
Wang, Zhiyu [5 ]
Lizee, Gregory [4 ,6 ]
机构
[1] Tianjin BeiChen Hosp, Core Lab, Beiyi Rd, Tianjin 300400, Peoples R China
[2] Tianjin Beichen Hosp, Dept Pathol, Tianjin, Peoples R China
[3] Tianjin Beichen Hosp, Dept Neurosurg, Tianjin 300400, Peoples R China
[4] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77054 USA
[5] Hebei Med Univ, Dept Immunooncol, Hosp 4, Shijiazhuang 050011, Peoples R China
[6] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA
关键词
epidermal growth factor receptor; peptide vaccine; lung cancer; immunotherapy; DOUBLE-BLIND; PHASE-II; EGFR; VARIANT; RINDOPEPIMUT; MUTANT; UBIQUITINATION; IMMUNOTHERAPY; ACTIVATION; THERAPY;
D O I
10.3390/vaccines11091460
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 EGFR 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.
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页数:16
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