The use of genetically modified cell products for cancer treatment is one of the most actively developing areas of biomedicine. The generation of such cell products is not a purely technical task, since, as in addition to well-established biotechnological processes, a deep understanding of the biology of effector lymphocytes and cancer cells is required. One example is CAR T-cell therapy for hematological malignancies.
Although the US FDA approved three such CAR T-cell products for some hematological malignancies (B-r/rALL, NHL), the long-term survival of patients without subsequent bone marrow transplantation is on average no better than 30-40%. Moreover, in relation to other hematological malignancies, in particular MDS, AML, T-ALL, the results of CAR T-cell therapy are even worse. Therefore, it seems extremely important: a) to study the basic principles of T-/NK-cell activation and the interaction of these cells with tumor cells; b) to obtain new proteins that recognize cancer determinants on tumor cells; c) to develop new generation CAR T- and NK-cell products, including allogeneic ones, to ensure stable remission and complete recovery in these patients.
It is well known that the current effectiveness of cell therapy in the context of most solid cancers is low and requires the development of new solutions for the CAR structure, ancillary modules, production of cell products, as well as the search for effective therapeutic combinations. The research carried out in the laboratory is complex and relevant, and the results are in demand by the medical community and, most importantly, by patients. It should be noted that, in addition to the obvious translational importance, the work will also provide fundamental data.
Major publications
Shuvalov O., Kizenko A., Petukhov A., Aksenov N., Fedorova O., Vorobev M., Daks A., Barlev N. Cancer-testis antigens, semenogelins 1 and 2, exhibit different anti-proliferative effects on human lung adenocarcinoma cells. Cell Death Discov. 2020;6:108. doi: 10.1038/s41420-020-00336-5. eCollection 2020. PubMed PMID: 33101710; PubMed Central PMCID: PMC7581521.
Fedorova O., Daks A., Shuvalov O., Kizenko A., Petukhov A., Gnennaya Y., Barlev N. Attenuation of p53 mutant as an approach for treatment Her2-positive cancer. Cell Death Discov. 2020;6:100. doi: 10.1038/s41420-020-00337-4. eCollection 2020. Review. PubMed PMID: 33083021; PubMed Central PMCID: PMC7548004.
Vasileva E., Shuvalov O., Petukhov A., Fedorova O., Daks A., Nader R., Barlev N. KMT Set7/9 is a new regulator of Sam68 STAR-protein. Biochem Biophys Res Commun. 2020 May 14;525(4):1018-1024. doi: 10.1016/j.bbrc.2020.03.017. Epub 2020 Mar 13. PubMed PMID: 32178870.
Titov A., Valiullina A., Zmievskaya E., Zaikova E., Petukhov A., Miftakhova R., Bulatov E., Rizvanov A. Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment. Cancers (Basel). 2020 Jan 3;12(1). doi: 10.3390/cancers12010125. Review. PubMed PMID: 31947775; PubMed Central PMCID: PMC7016531.
Deryabin P., Griukova A., Shatrova A., Petukhov A., Nikolsky N., Borodkina A. Optimization of lentiviral transduction parameters and its application for CRISPR-based secretome modification of human endometrial mesenchymal stem cells. Cell Cycle. 2019 Mar - Apr;18(6-7):742-758. doi: 10.1080/15384101.2019.1593650. Epub 2019 Mar 28. PubMed PMID: 30880567; PubMed Central PMCID: PMC6464586.
Fedorova O., Petukhov A., Daks A., Shuvalov O., Leonova T., Vasileva E., Aksenov N., Melino G., Barlev N. A. Orphan receptor NR4A3 is a novel target of p53 that contributes to apoptosis. Oncogene. 2019 Mar; 38(12): 2108-2122. doi: 10.1038/s41388-018-0566-8. Epub 2018 Nov 19. PubMed PMID: 30455429.
Suvorova I. I., Knyazeva A. R., Petukhov A. V., Aksenov N. D., Pospelov V. A. Resveratrol enhances pluripotency of mouse embryonic stem cells by activating AMPK/Ulk1 pathway. Cell Death Discov. 2019;5:61. doi: 10.1038/s41420-019-0137-y. eCollection 2019. PubMed PMID: 30729040; PubMed Central PMCID: PMC6361884.
Bulatov E., Sayarova R., Mingaleeva R., Miftakhova R., Gomzikova M., Ignatyev Y., Petukhov A., Davidovich P., Rizvanov A., Barlev N. A. Isatin-Schiff base-copper (II) complex induces cell death in p53-positive tumors. Cell Death Discov. 2018;4:103. doi: 10.1038/s41420-018-0120-z. eCollection 2018. PubMed PMID: 30455989; PubMed Central PMCID: PMC6234212.
Fedorova O., Daks A., Petrova V., Petukhov A., Lezina L., Shuvalov O., Davidovich P., Kriger D., Lomert E., Tentler D., Kartsev V., Uyanik B., Tribulovich V., Demidov O., Melino G., Barlev N. A. Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote apoptosis. Cell Cycle. 2018;17(15):1917-1930. doi: 10.1080/15384101.2018.1506664. Epub 2018 Sep 5. PubMed PMID: 30109812; PubMed Central PMCID: PMC6152504.
Titov A., Petukhov A., Staliarova A., Motorin D., Bulatov E., Shuvalov O., Soond S. M., Piacentini M., Melino G., Zaritskey A., Barlev N. A. The biological basis and clinical symptoms of CAR-T therapy-associated toxicites. Cell Death Dis. 2018 Sep 4;9(9):897. doi: 10.1038/s41419-018-0918-x. Review. PubMed PMID: 30181581; PubMed Central PMCID: PMC6123453.
Canfarotta F., Lezina L., Guerreiro A., Czulak J., Petukhov A., Daks A., Smolinska-Kempisty K., Poma A., Piletsky S., Barlev N. A. Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor. Nano Lett. 2018 Aug 8;18(8):4641-4646. doi: 10.1021/acs.nanolett.7b03206. Epub 2018 Jul 9. PubMed PMID: 29969563.
Kalinin R. S., Petukhov A. V., Knorre V. D., Maschan M. A., Stepanov A. V., Gabibov A. G. Molecular Approaches to Safe and Controlled Engineered T-cell Therapy. Acta Naturae. 2018 Apr-Jun;10(2):16-23. PubMed PMID: 30116611; PubMed Central PMCID: PMC6087824.
Kulemzin S. V., Gorchakov A. A., Chikaev A. N., Kuznetsova V. V., Volkova O. Y., Matvienko D. A., Petukhov A. V., Zaritskey A. Y., Taranin A. V. VEGFR2-specific FnCAR effectively redirects the cytotoxic activity of T cells and YT NK cells. Oncotarget. 2018 Feb 6;9(10):9021-9029. doi: 10.18632/oncotarget.24078. eCollection 2018 Feb 6. PubMed PMID: 29507671; PubMed Central PMCID: PMC5823625.
Lomert E., Turoverova L., Kriger D., Aksenov N. D., Nikotina A. D., Petukhov A., Mittenberg A. G., Panyushev N. V., Khotin M., Volkov K., Barlev N. A., Tentler D. Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells. Cell Cycle. 2018;17(5):616-626. doi: 10.1080/15384101.2017.1417709. Epub 2018 Jan 22. PubMed PMID: 29251177; PubMed Central PMCID: PMC5969568.
Shuvalov O., Kizenko A., Shakirova A., Fedorova O., Petukhov A., Aksenov N., Vasileva E., Daks A., Barlev N. Nutlin sensitizes lung carcinoma cells to interferon-alpha treatment in MDM2-dependent but p53-independent manner. Biochem Biophys Res Commun. 2018 Jan 1;495(1):1233-1239. doi: 10.1016/j.bbrc.2017.11.118. Epub 2017 Nov 23. PubMed PMID: 29175211.
Shuvalov O., Petukhov A., Daks A., Fedorova O., Vasileva E., Barlev N. A. One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy. Oncotarget. 2017 Apr 4;8(14):23955-23977. doi: 10.18632/oncotarget.15053. Review. PubMed PMID: 28177894; PubMed Central PMCID: PMC5410357.
Daks A., Petukhov A., Fedorova O., Shuvalov O., Merkulov V., Vasileva E., Antonov A., Barlev N. A. E3 ubiquitin ligase Pirh2 enhances tumorigenic properties of human non-small cell lung carcinoma cells. Genes Cancer. 2016 Nov;7(11-12):383-393. doi: 10.18632/genesandcancer.123. PubMed PMID: 28191284; PubMed Central PMCID: PMC5302039.