School of Medicine, Nankai University, Tianjin, China.
Department of Oncology, Oncology Laboratory, Chinese PLA General Hospital, Beijing, China.
Immun Inflamm Dis. 2023 Jan;11(1):e752. doi: 10.1002/iid3.752.
With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant.
In this study, bioinformatic methods, peptide exchange assay, and peptide-immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation.
Peptides with higher affinity to common HLA-A alleles (A11:01, A02:01) were discovered by computational prediction. All the 8-11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA-A2 transgenic mice model.
We identified three potential neoepitopes of p53 for HLA-A02:01, one potential neoepitope for HLA-A11:01 and no neoepitope for HLA-A*24:02.
随着基于癌症新生抗原的免疫疗法的兴起，鉴定新生肽段已成为亟待解决的问题。TP53 R273C 突变是 TP53 热点突变之一，但该突变的免疫原性尚不清楚。本研究旨在鉴定 p53R273C 突变潜在的表位。
本研究采用生物信息学方法、肽交换实验和肽免疫人白细胞抗原（HLA）转基因小鼠模型来探索该突变的免疫原性。
通过计算预测发现了与常见 HLA-A 等位基因（A11:01、A02:01）具有更高亲和力的肽段。所有包含突变位点的 8-11 个氨基酸肽段均已合成，可溶性肽段用于肽交换实验。然而，这些预测肽段与 HLA 的交换效率较低。幸运的是，发现了其他具有更高交换效率的肽段。然后，使用 HLA-A2 转基因小鼠模型验证了这些肽段的免疫原性。
我们鉴定了 p53 针对 HLA-A02:01 的三个潜在新表位、针对 HLA-A11:01 的一个潜在新表位和针对 HLA-A*24:02 的无新表位。
