Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients' T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).

中文翻译：

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NSCLC患者中肿瘤抗原和肿瘤抗原特异性T细胞的检测：T细胞反应质量与NSCLC亚型的相关性。

同种异体癌细胞系是癌症疫苗中肿瘤相关抗原的普遍来源。源自细胞系的免疫原性高静水压杀死的癌细胞可用于非小细胞肺癌（NSCLC）的基于树突细胞（DC）的主动细胞免疫疗法的产生。我们调查了12种已知的NSCLC肿瘤相关抗原（TAA）（CEA，MAGE-A1，MAGE-A3，MAGE-A4，PRAME，hTERT，HER2，MUC1，Survivin，STEAP1，SOX2和NY-ESO-1）的表达在6种NSCLC细胞系中作为候选药物，用于产生基于DC的肺癌疫苗。我们显示，这些细胞系的选定抗原谱与原发性NSCLC肿瘤的抗原谱有不同程度的重叠（n = 52），表明6种NSCLC细胞株中有4种适合基于DC的疫苗生成。我们在体外刺激试验中使用市售肽混合物进一步研究了NSCLC患者（n = 32）血液中TAA特异性T细胞的存在。在NSCLC患者中检测到IFN-γ+ CD8 +和IFN-γ+ CD4 + T细胞对所有抗原的反应。有趣的是，尽管鳞状细胞癌（SCC）中TAA的表达较高，但SCC患者中患者T细胞对刺激的反应性却明显低于腺癌（AC）患者。这暗示了NSCLC亚型之间的T细胞功能的质性差异。基于这项研究，为了使可治疗的患者数量最大化，我们选择了H520和H522 NSCLC细胞系的混合物用于基于DC的疫苗制备。我们还建立了最小限度的抗原肽混合物（CEA，hTERT，PRAME，