PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Case Report: Pathological Complete Response in a Lung Metastasis of Phyllodes Tumor Patient Following Treatment Containing Peptide Neoantigen Nano-Vaccine.
Case Report: Pathological Complete Response in a Lung Metastasis of Phyllodes Tumor Patient Following Treatment Containing Peptide Neoantigen Nano-Vaccine.
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基因突变转录和翻译产生的一些突变肽具有诱导特异性T细胞的能力,这些被称为新抗原。基于新抗原的肽、DNA、RNA和树突状细胞疫苗已在临床上使用。本文描述了一例叶状肿瘤患者的肺转移,在接受包含个性化多表位肽新抗原纳米疫苗的治疗后,表现出病理完全缓解。基于全外显子测序(WES)、RNA测序和新抗原预测,预测到几个突变肽片段能与患者的人类白细胞抗原(HLA)同种异型结合,其中包括十个对六个基因具有高预测结合亲和力的肽。在四个周期的抗PD1和安罗替尼治疗后,肺转移灶保持稳定。在加入多表位肽新抗原纳米疫苗后,肿瘤开始塌陷并出现挛缩,伴随肿瘤标志物降至正常,并实现了完全病理缓解。在使用疫苗时,每次均使用重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF),并每3周注射低剂量环磷酰胺以提高疗效。外周血免疫监测显示对一系列肽具有免疫反应性,其中疫苗后T细胞反应最强的是针对HLA-DRB1*0901限制性的SLC44A5 V54F肽。
Some of the mutant peptides produced by gene mutation transcription and translation have the ability to induce specific T cells, which are called new antigens. Neoantigen-based peptide, DNA, RNA, and dendritic cell vaccines have been used in the clinic. In this paper, we describe a lung metastasis of a phyllodes tumor patient demonstrating pathological complete response following treatment containing personalized multi-epitope peptide neoantigen nano-vaccine. Based on whole-exome sequencing (WES), RNA sequencing, and new antigen prediction, several mutated peptide fragments were predicted to bind to the patient's human leukocyte antigen (HLA) allotypes, including ten peptides with high predicted binding affinity for six genes.
The pulmonary metastases remained stable after the four cycles of anti-PD1 and anlotinib. After the addition of the multi-epitope peptide neoantigen nano-vaccine, the tumor began to collapse and contracture developed, accompanied by a decrease of tumor markers to normal, and complete pathological remission was achieved.
With the use of the vaccination, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was used every time, and low-dose cyclophosphamide was injected every 3 weeks to improve efficacy. Peripheral blood immune monitoring demonstrated immune reactivity against a series of peptides, with the most robust post-vaccine T-cell response detected against the HLA-DRB1*0901-restricted SLC44A5 V54F peptide.
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