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

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 

机构地区：[1]Institute of Cytology and Genetics,Siberian Branch of the Russian Academy of Sciences,Novosibirsk 630090,Russia [2]Department of Natural Sciences,Novosibirsk State University,Novosibirsk 630090,Russia [3]Department of Physics,Novosibirsk State University,Novosibirsk 630090,Russia [4]Department of Chemistry,Moscow State University,Moscow 119991,Russia [5]Research Institute of Fundamental and Clinical Immunology,Novosibirsk,630099,Russia

出　　处：《The Journal of Biomedical Research》2023年第3期194-212,共19页生物医学研究杂志（英文版）

基　　金：supported by the Russian Ministry of Science and High Education via the Institute of Cytology and Genetics (State Budget Project No.FWNR-2022-0016);the Russian Foundation for Basic Research (Grant No.18-29-09045).

摘　　要：To overcome immune tolerance to cancer,the immune system needs to be exposed to a multi-target action intervention.Here,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 vivo.Comparative 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 conducted.Antibodies against programmed death 1(PD1)checkpoint inhibitors or their corresponding PD1 DNA aptamers were also added to vaccination regimens for analytical purposes.Four 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 mice.Adding anti-PD1 antibodies(CpG+αOX40+αPD1)to in situ vaccinations boosts the antitumor effect.When to be used instead of antibodies,aptamers also possess antitumor activity,although this effect was less pronounced.The 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 

分 类 号：R730.5[医药卫生—肿瘤]