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Antitumor efficacy of multi-target in situ vaccinations with CpG oligodeoxynucleotides,anti-OX40,anti-PD1 antibodies,and aptamers

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The Journal of Biomedical research 2023年第3期37卷 194-212页

作者： Anastasia S.Proskurina Vera S.ruzanova Genrikh S.ritter Yaroslav r.Efremov Zakhar S.Mustafin Sergey A.Lashin Ekaterina A.Burakova Alesya A.Fokina Timofei S.Zatsepin Dmitry A.Stetsenko Olga Y.Leplina Alexandr A.Ostanin elena r.chernykh Sergey S.Bogachev Institute of Cytology and Genetics Siberian Branch of the Russian Academy of SciencesNovosibirsk 630090Russia Department of Natural Sciences Novosibirsk State UniversityNovosibirsk 630090Russia Department of Physics Novosibirsk State UniversityNovosibirsk 630090Russia Department of Chemistry Moscow State UniversityMoscow 119991Russia research Institute of Fundamental and Clinical Immunology Novosibirsk630099Russia

To overcome immune tolerance to cancer,the immune system needs to be exposed to a multi-target action ***,we investigated the activating effect of CpG oligodeoxynucleotides(ODNs),mesyl phosphoramidate CpG ODNs,anti-OX40 antibodies,and OX40 rNA aptamers on major populations of immunocompetent cells ex *** analysis of the antitumor effects of in situ vaccination with CpG ODNs and anti-OX40 antibodies,as well as several other combinations,such as mesyl phosphoramidate CpG ODNs and OX40 rNA aptamers,was *** against programmed death 1(PD1)checkpoint inhibitors or their corresponding PD1 DNA aptamers were also added to vaccination regimens for analytical *** scenarios were considered:a weakly immunogenic Krebs-2 carcinoma grafted in CBA mice;a moderately immunogenic Lewis carcinoma grafted in C57Black/6 mice;and an immunogenic A20 B cell lymphoma or an Ehrlich carcinoma grafted in BALB/c *** anti-PD1 antibodies(CpG+αOX40+αPD1)to in situ vaccinations boosts the antitumor *** to be used instead of antibodies,aptamers also possess antitumor activity,although this effect was less *** strongest effect across all the tumors was observed in highly immunogenic A20 B cell lymphoma and Ehrlich carcinoma.

关键词： immunogenicity Krebs-2 carcinoma Lewis carcinoma Ehrlich carcinoma A20 B cell lymphoma mesyl phosphoramidate

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Efficacy of the new therapeutic approach in curing malignant neoplasms on the model of human glioblastoma

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Cancer Biology & Medicine 2021年第3期18卷 910-930页

作者： Evgeniya V.Dolgova Oleg M.Andrushkevich Polina E.Kisaretova Anastasia S.Proskurina Genrikh S.ritter Tatyana D.Dubatolova Margarita V.romanenko Oleg S.Taranov Yaroslav r.Efremov Evgeniy L.Zavyalov Alexandr V.romaschenko Sergey V.Mishinov Svetlana S.Kirikovich Evgeniy V.Levites Ekaterina A.Potter Alexandr A.Ostanin elena r.chernykh Stanislav Yu.roshchin Anatoliy V.Bervitskiy Galina I.Moysak Jamil A.rzaev Sergey S.Bogachev Institute of Cytology and Genetics SB rAS Novosibirsk 630090Russia A.I.Evdokimov Moscow State University of Medicine and Dentistry Moscow 127473Russia Institute of Molecular and Cellular Biology Novosibirsk 630090Russia Novosibirsk State University Novosibirsk 630090Russia The State research Center of Virology and Biotechnology"Vector" KoltsovoNovosibirsk 630559Russia First Department of Neurosurgery Ya.L.Tsivian Novosibirsk Research Institute of Traumatology and OrthopaedicsNovosibirsk 630091Russia Institute of Fundamental and Clinical immunology Novosibirsk 630099Russia Sklifosovsky research Institute of Emergency Medicine Moscow 129010Russia Federal Center of Neurosurgery Novosibirsk 630048Russia

Objective:Glioma is a highly invasive tumor,frequently disposed in essential areas of the brain,which makes its surgical excision extremely difficult;meanwhile adjuvant therapy remains quite ***:In the current report,a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma *** approach,termed"Karanahan",is aimed at the eradication of cancer stem cells(CSCs),which were recently shown to be capable of internalizing fragments of extracellular double-stranded *** being internalized,these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics,and such an interference results either in elimination of CSCs or in the loss of their tumorigenic *** of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA ***:U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient *** SCID mice with developed subcutaneous grafts,the treatment resulted in reliable slowing down of tumor growth rate(Priment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment,the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the ***:The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.

关键词： Glioblastoma U87 cell line mytomycin C cancer stem cells TAMrA

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Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis

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Asian Journal of Andrology 2018年第6期20卷 593-599页

作者： Ilya S Dantsev Evgeniy V Ivkin Aleksey A Tryakin Dmitriy N Godlevski Oleg Yu Latyshev Victoriya V rudenko Dmitry S Mikhaylenko Vyacheslav B chernykh elena A Volodko Aleksey B Okulov Oleg B Loran Marina V Nemtsova russian Medical Academy ef Postgraduate Education Moscow 123995 Russia N. N. Blokhin russian Cancer research Center Moscow 115478 Russia research Centre of Medical Genetics Moscow 115478 Russia I. M. Sechenov First Moscow State Medical University Moscow 119991 Russia N. I. Pirogov russian National research Medical University Moscow 117997 Russia.

Testicular microlithiasis （TM） is one of the symptoms of testicular dysgenesis syndrome （TDS）. TM is particularly interesting as an informative marker of testicular germ cell tumors （TGCTs）. KIT ligand gene （KITLG）, BCL2 antagonist/killer 1 （BAK1）, and sprouty rTK signaling antagonist 4 （SPrY4） genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene （BMP7）, transforming growth factor beta receptor 3 gene （TGFBr3）, and homeobox D cluster genes （HOXD） are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism （PCr-rFLP） analysis, we investigated allele and genotype frequencies for KITLG （rs995030, rs1508595）, SPrY4 （rs4624820, rs6897876）, BAK1 （rs210138）, BMP7 （rs388286）, TGFBr3 （rs12082710）, and HOXD （rs17198432） in 142 TGCT patients, 137 TM patients, and 153 fertile men （control group）. We found significant differences in the KITLG GG_rs995030 genotype in TM （P= 0.01） and TGCT patients （P = 0.0005） compared with the control. We also revealed strong associations between KITLGrs1508595 and TM （G allele, P = 0.003; GG genotype, P= 0.01） and between KITLG_rs1508595 and TGCTs （G allele, P-- 0.0001; GG genotype, P = 0.0007）. Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control （T allele, P = 0.00004; TT genotype, P = 0.00006） and between the TM group and the control （T allele, P= 0.04）. HOXDalso demonstrated a strong association with TGCTs （rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001）. Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele （P= 0.03） and the GG genotype （P= 0.01）. KITLG and BMP7genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.

关键词： associations genotype high risk testicular dysgenesis syndrome testicular microlithiasis

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