以下是目前公布的、已通过T细胞识别验证的胰腺癌抗原肽清单，该清单均支持定制生产抗原肽MHC四聚体，用于捕获抗原特异性T细胞。可应用于：
- 检测或分选抗原特异性T细胞的流式试剂、磁珠分选试剂
- 构建抗原肽和MHC复合物，用于合成人工呈递物，从而刺激T细胞
| 抗原肽 | 抗原蛋白 | 呈递的HLA | 验证文献 |
|---|---|---|---|
| MQTSEREGSGPELSPSVM | Spastic paraplegia 33 protein, Zinc finger FYVE domain-containing protein 27, ZFYVE27, SPG33 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers.; Science; 2015 Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers.; Cancer Discov; 2019 |
| TLMDMRLSQVSDSVSGQTVVDPKGY | Androgen receptor N-terminal domain-transactivating protein 1, PRP6 homolog, U5 snRNP-associated 102 kDa protein, PRPF6, C20orf14 | HLA class I | Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers.; Cancer Discov; 2019 |
| GPQETLDRTVHCQPAIFVASLAAVE | Mitochondrial malonyl CoA:ACP acyltransferase, Mitochondrial malonyltransferase, [Acyl-carrier-protein] malonyltransferase, MCAT, MT | HLA class I | Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers.; Cancer Discov; 2019 |
| LLMREVPLRCTIRLWDTYQSEPDGF | TBC1D22A, C22orf4 | HLA-A*01:01 | Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation.; Genome Med; 2021 |
| LVRAVQFTETFLTERDKQSKWSGIP | Protein TAP1, TNF-receptor ubiquitous scaffolding/signaling protein, TRPC4AP, C20orf188, TRRP4AP | HLA-B*44:03 | Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation.; Genome Med; 2021 |
| HTGEKPYRCKVCDTAFTWHSQLARH | ZNF611 | HLA-A*32:01 | Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation.; Genome Med; 2021 |
| VVVGAGGVG | KRAS | HLA-B35 | Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation.; Int J Cancer; 1997 |
| VVGAGGVGK | KRAS | HLA-A*11:01 | Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.; Cancer Immunol Immunother; 2022 |
| VVVGAGGVGK | KRAS | HLA-A*11:01 | Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.; Cancer Immunol Immunother; 2022 |
| GADGVGKSA | KRAS | HLA-C*08:02 | Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer. N Engl J Med . 2022 |
| GADGVGKSAL | KRAS | HLA-C*08:02 | Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer. N Engl J Med . 2022 |
该清单中，最著名的是KRAS G12突变，该突变在胰腺癌方面呈现免疫原性，同时也是肺癌小分子靶向治疗的热门靶点。在靶向KRAS G12D突变的抗原肽方面，诱导高丰度表达专一性TCR的T细胞，具有强烈对KRAS G12D的杀伤效应。
胰腺癌抗原清单使用方法：
肿瘤微环境研究：检测肿瘤浸润淋巴细胞中，肿瘤抗原特异性淋巴细胞的数量实现。具体方式是：根据清单内容，将抗原肽和HLA合成为抗原肽MHC复合物荧光四聚体，通过流式细胞检测方法，检测肿瘤浸润淋巴细胞的含量。
肿瘤免疫细胞的全身分布：
通过检测外周血中肿瘤抗原特异性淋巴细胞的数量实现。具体方法同上。
过继性肿瘤免疫细胞治疗：
使用清单中抗原肽，刺激淋巴细胞，而后使用抗原肽MHC复合物荧光四聚体或磁珠四聚体，通过流式分选或磁珠分选细胞，经体外细胞增殖后，回输体内，评估肿瘤抑制效果。
肿瘤抗原特异性TCR测序：
通过肿瘤浸润淋巴细胞、或外周血淋巴细胞，通过分选后进行单细胞TCR测序，获得抗原特异性T细胞的TCR序列，进一步进行TCR-T疗法研究。
肿瘤疫苗片段筛选：
综合上述过程，获得具有激活T细胞杀伤肿瘤细胞的经验证抗原肽MHC复合物，用于肿瘤疫苗构建。
