Danilova Anna, Misyurin Vsevolod, Novik Aleksei, Girdyuk Dmitry, Avdonkina Natalia, Nekhaeva Tatiana, Emelyanova Natalia, Pipia Nino, Misyurin Andrey, Baldueva Irina
1N.N. Petrov' National Medical Cancer Research Center, Leningradskaya str., 68, Pesochniy, Saint-Petersburg, 197758 Russian Federation.
3Department of Oncoimmunology, N.N. Petrov' National Medical Cancer Research Center, Leningradskaya str., 68, Pesochniy, Saint-Petersburg, 197758 Russian Federation.
Clin Sarcoma Res. 2020 Feb 4;10:3. doi: 10.1186/s13569-020-0125-2. eCollection 2020.
BACKGROUND: Autologous dendritic cells (DC) loaded with tumor-associated antigens (TAAs) are a promising approach for anticancer immunotherapy. Polyantigen lysates appear to be an excellent source of TAAs for loading onto the patient's dendritic cells. Cancer/testis antigens (CTA) are expressed by a wide range of tumors, but are minimally expressed on normal tissues, and could serve as a universal target for immunotherapy. However, CTA expression levels can vary significantly in patients with the same tumor type. We proposed that patients who do not respond to DC-based therapy may have distinct features of the CTA expression profile on tumor cells. PATIENTS AND METHODS: We compared the gene expression of the principal families CTA in 22 melanoma and 27 soft tissue and bone sarcomas cell lines (STBS), received from patients and used for DC vaccine preparation. RESULTS: The majority (47 of 49, 95.9%) cell lines showed CTA gene activity. The incidence of gene expression of , , , 's was significantly different (adj. p < 0.05) between melanoma and sarcoma cell lines. The expression of the gene was detected neither in melanoma cells nor in the STBS cells. Clustering by the gene expression profile revealed four different expression patterns. We found three main patterns types: hyperexpression of multiple CTA, hyperexpression of one CTA with almost no expression of others, and no expression of CTA. All clusters types exist in melanoma and sarcoma cell lines. We observed dependence of killing efficacy from the (rho = 0.940, adj. p < 0.01) expression during real-time monitoring with the xCELLigence system of the interaction between melanoma or sarcoma cells with the T-lymphocytes activated by the lysate of selected allogenous melanoma cell lines with high expression of CTA. CONCLUSION: Our results demonstrate that one can use lysates from allogeneic melanoma cell lines as a source of CTA for DC load during the production of anticancer vaccines for the STBS treatment. Patterns of CTA expression should be evaluated as biomarkers of response in prospective clinical trials.
背景：负载肿瘤相关抗原（TAA）的自体树突状细胞（DC）是抗癌免疫治疗的一种有前景的方法。多抗原裂解物似乎是用于负载患者树突状细胞的TAA的极佳来源。癌胚抗原（CTA）在多种肿瘤中表达，但在正常组织中表达极少，可作为免疫治疗的通用靶点。然而，相同肿瘤类型的患者中CTA表达水平可能有显著差异。我们推测对基于DC的治疗无反应的患者在肿瘤细胞上的CTA表达谱可能有独特特征。 患者和方法：我们比较了从患者处获得并用于制备DC疫苗的22株黑色素瘤细胞系以及27株软组织和骨肉瘤细胞系（STBS）中主要CTA家族的基因表达。 结果：大多数（49株中的47株，95.9%）细胞系显示CTA基因活性。黑色素瘤和肉瘤细胞系之间， 、 、 、 的基因表达发生率有显著差异（校正p < 0.05）。在黑色素瘤细胞和STBS细胞中均未检测到 基因的表达。根据基因表达谱聚类揭示了四种不同的表达模式。我们发现了三种主要模式类型：多种CTA的高表达、一种CTA的高表达而其他几乎不表达以及CTA不表达。所有聚类类型均存在于黑色素瘤和肉瘤细胞系中。在用xCELLigence系统实时监测黑色素瘤或肉瘤细胞与由选定的高表达CTA的同种异体黑色素瘤细胞系裂解物激活的T淋巴细胞之间的相互作用过程中，我们观察到杀伤效力与 （rho = 0.940，校正p < 0.01）表达的相关性。 结论：我们的结果表明，在制备用于STBS治疗的抗癌疫苗过程中，可将同种异体黑色素瘤细胞系的裂解物用作CTA来源以负载DC。在未来的临床试验中，CTA表达模式应作为反应的生物标志物进行评估。
Clin Sarcoma Res. 2020-2-4
Hum Vaccin Immunother. 2014
Cancer Immunol Immunother. 2018-3-29
J Pers Med. 2021-9-9
Melanoma Res. 2019-8
Cancer Treat Rev. 2018-10-25
Semin Cell Dev Biol. 2018-3-21
Immunotherapy. 2017-10
Expert Rev Clin Immunol. 2017-8-23
Zotero 插件