<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">dan</journal-id><journal-title-group><journal-title xml:lang="ru">Доклады Национальной академии наук Беларуси</journal-title><trans-title-group xml:lang="en"><trans-title>Doklady of the National Academy of Sciences of Belarus</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1561-8323</issn><issn pub-type="epub">2524-2431</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29235/1561-8323-2024-68-6-465-473</article-id><article-id custom-type="elpub" pub-id-type="custom">dan-1223</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Разработка лентивирусной векторной системы для эктопической экспрессии и презентации меланомного антигена MLANA в клетках человека</article-title><trans-title-group xml:lang="en"><trans-title>Development of the lentivirusbased vector system for ectopic expression and presentation of the melanoma antigen MLANA in human cells</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9535-7157</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Антоневич</surname><given-names>Н. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Antonevich</surname><given-names>N. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Антоневич Наталья Георгиевна – канд. биол. наук, доцент, вед. науч. сотрудник</p><p>ул. Академическая, 27, 220072, Минск</p></bio><bio xml:lang="en"><p>Antonevich Natalia G. – Ph. D. (Biology), Associate Professor, Leading Researche</p><p>27, Akademicheskaya Str., 220072, Minsk</p></bio><email xlink:type="simple">antonevich.n@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-8909-2767</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бадалян</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Badalyan</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бадалян Ирина Артуровна – мл. науч. сотрудник</p><p>ул. Академическая, 27, 220072, Минск</p></bio><bio xml:lang="en"><p>Badalyan Iryna A. – Junior Researcher</p><p>27, Akademicheskaya Str., 220072, Minsk</p></bio><email xlink:type="simple">irina1512.37533@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4869-9864</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гончаров</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Hancharou</surname><given-names>A. Y.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гончаров Андрей Евгеньевич – канд. мед. наук, доцент, директор</p><p>ул. Академическая, 27, 220072, Минск</p></bio><bio xml:lang="en"><p>Hancharou Andrei Y. – Ph. D. (Medicine), Associate Professor, Director</p><p>27, Akademicheskaya Str., 220072, Minsk</p></bio><email xlink:type="simple">andrei.hancharou@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4524-3730</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Титов</surname><given-names>Л. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Titov</surname><given-names>L. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Титов Леонид Петрович – академик, д-р мед. наук, профессор, гл. науч. сотрудник</p><p>ул. Казинца, 50, 220099, Минск</p></bio><bio xml:lang="en"><p>Titov Leonid P. – Academician, D. Sc. (Medicine), Professor, Chief Researcher</p><p>50, Kazinets Str., 220099, Minsk</p></bio><email xlink:type="simple">leotit310@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9981-7333</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гринев</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Grinev</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гринев Василий Викторович – канд. биол. наук, доцент</p><p>ул. Курчатова, 10, 220045, Минск</p></bio><bio xml:lang="en"><p>Grinev Vasily V. – Ph. D. (Biology), Associate Professor</p><p>10, Kurchatov Str., 220045, Minsk</p></bio><email xlink:type="simple">grinev_vv@bsu.by</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Институт биофизики и клеточной инженерии Национальной академии наук Беларуси</institution></aff><aff xml:lang="en"><institution>Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Республиканский центр гигиены, эпидемиологии и общественного здоровья</institution></aff><aff xml:lang="en"><institution>Republican Center for Hygiene, Epidemiology and Public Health</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Белорусский государственный университет</institution></aff><aff xml:lang="en"><institution>Belarusian State University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>08</day><month>01</month><year>2025</year></pub-date><volume>68</volume><issue>6</issue><fpage>465</fpage><lpage>473</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Антоневич Н.Г., Бадалян И.А., Гончаров А.Е., Титов Л.П., Гринев В.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Антоневич Н.Г., Бадалян И.А., Гончаров А.Е., Титов Л.П., Гринев В.В.</copyright-holder><copyright-holder xml:lang="en">Antonevich N.G., Badalyan I.A., Hancharou A.Y., Titov L.P., Grinev V.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://doklady.belnauka.by/jour/article/view/1223">https://doklady.belnauka.by/jour/article/view/1223</self-uri><abstract><p>Освоены и испытаны лентивирусные векторы экспрессии, кодирующие два генно-инженерных варианта белка MLANA, названных MLANA-FLAG® и MLANA-FLAG®-LAMP1. Транскрипционная/трансляционная активность сконструированных последовательностей в клетках линии HEK 293T и дендритных клетках подтверждена методами флуоресцентной конфокальной микроскопии и проточной цитометрии. Созданные генетические конструкции могут быть использованы для генетической модификации дендритных клеток и разработки новых методов клеточной терапии меланомы.</p></abstract><trans-abstract xml:lang="en"><p>Lentivirus-based vectors encoding two engineered melanoma associated MLANA proteins, named MLANAFLAG® and MLANA-FLAG®-LAMP1, were developed and tested. Transcriptional and translational activity of engineered proteins was confirmed in HEK 293T cells and dendritic cells by fluorescence confocal microscopy and flow cytometry. These new vectors can be used for lentiviral transduction of dendritic cells and the creation of new cell therapies for human melanoma.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>меланома</kwd><kwd>белок MLANA</kwd><kwd>лентивирусная трансдукция</kwd><kwd>дендритные клетки</kwd><kwd>презентация антигена</kwd></kwd-group><kwd-group xml:lang="en"><kwd>melanoma</kwd><kwd>MLANA protein</kwd><kwd>lentiviral transduction</kwd><kwd>dendritic cells</kwd><kwd>antigen presentation</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при поддержке гранта на исследование 1.17 ГПНИ «Биотехнологии-2» (№ 20220247 от 10.03.2022).</funding-statement><funding-statement xml:lang="en">This research was supported by project grant 1.17 of the State program of scientific research «Biotechnology-2» (No. 20220247 dated 10 March 2022).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Всемирный день борьбы с меланомой [Электронный ресурс]. – Режим доступа: https://minzdrav.gov.by/ru/novoe-na-sayte/vsemirnyy-den-borby-s-melanomoy/. – Дата доступа: 31.07.2024.</mixed-citation><mixed-citation xml:lang="en">World Melanoma Day. Available at: https://minzdrav.gov.by/ru/novoe-na-sayte/vsemirnyy-den-borby-s-melanomoy/ (accessed 20 June 2024) (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Efficacy of immune checkpoint inhibition in metastatic uveal melanoma: a systematic review and meta-analysis / J. P. Pham [et al.] // Melanoma Research. – 2023. – Vol. 33, N 4. – P. 316–325. https://doi.org/10.1097/cmr.0000000000000900</mixed-citation><mixed-citation xml:lang="en">Pham J. P., On L., Ardolino L., Hurwitz J., Salaun H., Sim H.-W., Joshua A. M. Efficacy of immune checkpoint inhibition in metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Research, 2023, vol. 33, no. 4, pp. 316–325. https://doi.org/10.1097/cmr.0000000000000900</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Gonzalez, H. Roles of the immune system in cancer: from tumor initiation to metastatic progression / H. Gonzalez, C. Hagerling, Z. Werb // Genes Dev. – 2018. – Vol. 32. – P. 1267–1284. https://doi.org/10.1101/gad.314617.118</mixed-citation><mixed-citation xml:lang="en">Gonzalez H., Hagerling C., Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes and Development, 2018, vol. 32, pp. 1267–1284. https://doi.org/10.1101/gad.314617.118</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Применение биомедицинского клеточного продукта на основе моноцитарных дендритных клеток в лечении пациентов, страдающих раком мочевого пузыря: результаты клинического исследования / А. Е. Гончаров [и др.] // БГМУ в авангарде медицинской науки и практики: сб. науч. тр. – Минск, 2021. – Вып. 11. – С. 205–215.</mixed-citation><mixed-citation xml:lang="en">Hancharou A. Y., Prokhorov A. V., Timohina O. V., Antonevich N. G., Minich Y. S., Rynda A. G., Prokhorov V. A. The use of a biomedical cell product based on monocytic dendritic cells in the treatment of bladder cancer patients: results of a clinical research. BGMU v avangarde meditsinskoi nauki i praktiki: sbornik nauchnykh trudov [BSMU at the forefront of medical science and practice: collection of scientific papers]. Minsk, 2021, iss. 11, pp. 205–215 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Dendritic Cell Vaccine Loaded with MG-7 Antigen Induces Cytotoxic T Lymphocyte Responses against Gastric Cancer / B. Zhu [et al.] // J. Healthc. Eng. – 2022. – Vol. 2022. – Art. 1964081. https://doi.org/10.1155/2022/1964081</mixed-citation><mixed-citation xml:lang="en">Zhu B., Sun Y., Wei X., Zhou H., Cao J., Li Ch., Wu N. Dendritic Cell Vaccine Loaded with MG-7 Antigen Induces Cytotoxic T Lymphocyte Responses against Gastric Cancer. Journal of Healthcare Engineering, 2022, vol. 2022, art. 1964081. https://doi.org/10.1155/2022/1964081</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma / R. Huang [et al.] // J. Healthc. Eng. – 2022. – Vol. 2022. – Art. 2518847. https://doi.org/10.1155/2022/2518847</mixed-citation><mixed-citation xml:lang="en">Huang R., Pan J., Zhang Y., Qin Q., Chao N., Huang T., Chen Ch., Zhao F., Luo G. GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma. Journal of Healthcare Engineering, 2022, vol. 2022, art. 2518847. https://doi.org/10.1155/2022/2518847</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">The melanocytic protein Melan-A/MART-1 has a subcellular localization distinct from typical melanosomal proteins / A. M. De Mazière [et al.] // Traffic. – 2002. – Vol. 3, N 9. – P. 678–693. https://doi.org/10.1034/j.1600-0854.2002.30909.x</mixed-citation><mixed-citation xml:lang="en">De Mazière A. M., Muehlethaler K., van Donselaar E., Salvi S., Davoust J., Cerottini J.-Ch., Lévy F., Slot J. W., Rimoldi D. The melanocytic protein Melan-A/MART-1 has a subcellular localization distinct from typical melanosomal proteins. Traffic, 2002, vol. 3, no. 9, pp. 678–693. https://doi.org/10.1034/j.1600-0854.2002.30909.x</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Высокоэффективный перенос и стабильная экспрессия двух генов при лентивирусной трансдукции мезенхимальных стволовых клеток костного мозга человека / В. В. Гринев [и др.] // Генетика. – 2012. – Т. 48, № 3. – P. 389–400.</mixed-citation><mixed-citation xml:lang="en">Grinev V. V., Seviaryn I. N., Posrednik D. V., Kosmacheva S. M., Potapnev M. P. Highly efficient transfer and stable expression of two genes upon lentivirus transduction of mesenchymal stem cells from human bone marrow. Russian Journal of Genetics, 2012, vol. 48, pp. 336–346. https://doi.org/10.1134/s1022795412030039</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Вирусные векторы для стабильной трансдукции мезенхимальных стволовых клеток человека: системы на основе аденоассоциированных вирусов и лентивирусов / А. В. Шахбазов [и др.] // Клеточные технологии в биологии и медицине. – 2008. – № 4. – P. 216–218.</mixed-citation><mixed-citation xml:lang="en">Shakhbazau A. V., Sevyaryn I. N., Goncharova N. V., Grinev V. V., Kosmacheva S. M., Potapnev M. P. Viral vectors for stable transduction of human mesenchymal stem cells: systems based on adeno-associated viruses and lentiviruses. Bulletin of Experimental Biology and Medicine, 2008, vol. 146, pp. 531–533. https://doi.org/10.1007/s10517-009-0320-x</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Protter: interactive protein feature visualization and integration with experimental proteomic data / U. Omasits [et al.] // Bioinformatics. – 2014. – Vol. 30, N 6. – P. 884–886. https://doi.org/10.1093/bioinformatics/btt607</mixed-citation><mixed-citation xml:lang="en">Omasits U., Ahrens Ch. H., Müller S., Wollscheid B. Protter: interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics, 2014, vol. 30, no. 6, pp. 884–886. https://doi.org/10.1093/bioinformatics/btt607</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">I-TASSER-MTD: a deep-learning-based platform for multi-domain protein structure and function prediction / X. Zhou [et al.] // Nat. Protoc. – 2022. – Vol. 17. – P. 2326–2353. https://doi.org/10.1038/s41596-022-00728-0</mixed-citation><mixed-citation xml:lang="en">Zhou X., Zheng W., Li Y., Pearce R., Zhang Ch., Bell E. W., Zhang G., Zhang Ya. I-TASSER-MTD: a deep-learningbased platform for multi-domain protein structure and function prediction. Nature Protocols, 2022, vol. 17, pp. 2326–2353. https://doi.org/10.1038/s41596-022-00728-0</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Park, H. CASP11 refinement experiments with ROSETTA / H. Park, F. DiMaio, D. Baker // Proteins: Structure, Function, and Bioinformatics. – 2016. – Vol. 84, N S1. – P. 314–322. https://doi.org/10.1002/prot.24862</mixed-citation><mixed-citation xml:lang="en">Park H., DiMaio F., Baker D. CASP11 refinement experiments with ROSETTA. Proteins: Structure, Function, and Bioinformatics, 2016, vol. 84, no. S1, pp. 314–322. https://doi.org/10.1002/prot.24862</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">GalaxyRefine2: simultaneous refinement of inaccurate local regions and overall protein structure / G. R. Lee [et al.] // Nucleic Acids Res. – 2019. – Vol. 47, N W1. – P. 451–455. https://doi.org/10.1093/nar/gkz288</mixed-citation><mixed-citation xml:lang="en">Lee G. R., Won J., Heo L., Seok Ch. GalaxyRefine2: simultaneous refinement of inaccurate local regions and overall protein structure. Nucleic Acids Research, 2019, vol. 47, no. W1, pp. 451–455. https://doi.org/10.1093/nar/gkz288</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Abualrous, E. T. Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation / E. T. Abualrous, J. Sticht, C. Freund // Curr. Opin. Immunol. – 2021. – Vol. 70. – P. 95–104. https://doi.org/10.1016/j.coi.2021.04.009</mixed-citation><mixed-citation xml:lang="en">Abualrous E. T., Sticht J., Freund C. Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation. Current Opinion in Immunology, 2021, vol. 70, pp. 95–104. https://doi.org/10.1016/j.coi.2021.04.009</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules / A. Bonehill [et al.] // J. Immunol. – 2004. – Vol. 172, N 11. – P. 6649–6657. https://doi.org/10.4049/jimmunol.172.11.6649</mixed-citation><mixed-citation xml:lang="en">Bonehill A., Heirman C., Tuyaerts S., Michiels A., Breckpot K., Brasseur F., Zhang Y., Van der Bruggen P., Thielemans K. Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules. Journal of Immunology, 2004, vol. 172, no. 11, pp. 6649–6657. https://doi.org/10.4049/jimmunol.172.11.6649</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
