The synergistic antitumor effect of Karanahan technology and in situ vaccination using anti-OX40 antibodies  

作　　者：VERA RUZANOVA ANASTASIA PROSKURINA GENRIKH RITTER EVGENIYA DOLGOVA SOFYA OSHIKHMINA SVETLANA KIRIKOVICH EVGENIY LEVITES YAROSLAV EFREMOV OLEG TARANOV ALEXANDR OSTANIN ELENA CHERNYKH NIKOLAY KOLCHANOV SERGEY BOGACHEV 

机构地区：[1]Laboratory of Induced Cellular Processes,Institute of Cytology and Genetics SB RAS,Novosibirsk,630090,Russia [2]Novosibirsk National Research State University,Novosibirsk,630090,Russia [3]Center for Shared Use of Microscopic Analysis of Biological Objects SB RAS,Institute of Cytology and Genetics SB RAS,Novosibirsk,630090,Russia [4]Department of Microscopic Research,State Research Center of Virology and Biotechnology“Vector”,Koltsovo,630559,Russia [5]Laboratory of Cellular Immunotherapy,Research Institute of Fundamental and Clinical Immunology,Novosibirsk,630099,Russia [6]Department of Systems Biology,Institute of Cytology and Genetics SB RAS,Novosibirsk,630090,Russia

出　　处：《Oncology Research》2025年第5期1229-1248,共20页肿瘤学研究(英文)

基　　金：supported by Inga N.Zaitseva;“Karanahan”LLC and the Ministry of Science and Higher Education of the Russian Federation via the Institute of Cytology and Genetics(State Budget Project No.FWNR-2022-0016).

摘　　要：Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depending on the characteristics of tumor cells,as well as the immune status.The main purpose of this study was to experimentally prove the feasibility of combining the Karanahan technology and in situ vaccination withαOX40 antibodies into a single therapeutic platform to achieve a potent additive antitumor therapeutic effect.Methods:BALB/c mice grafted with B-cellular lymphoma A20 were treated using the Karanahan technology consisting of intraperitoneal cyclophosphamide administrations and intratumoral DNA injections according to an individually determined therapeutic regimen,together with in situ vaccination withαOX40.A pathomorphological analysis of the organs of experimental animals that died during the initial attempt to combine the two technologies was carried out.An analysis of blood cell populations was performed to determine the safe time for antibody administration:the number of immune cells capable of activating systemic inflammation(CD11b+Ly-6C+,CD11b+Ly-6G+,CD3–NKp46+CD11b+),the presence of Fc receptor and OX40 on the surface of these cells,and the number of neutrophils activated to NETosis were analyzed.Based on the analysis results,the antitumor efficacy of various modes of combining the Karanahan technology and in situ vaccination was studied.Results:WhenαOX40 was administered 5 h after each treatment using the Karanahan technology,mass death of mice caused by systemic inflammation and multiple organ failure was observed.The state of blood cells after the treatment using the Karanahan technology at the time points corresponding to antibody injections was analyzed to elucidate the reasons for this effect.It was found that at some time points,there occurs activation of the immune system and a powerful release(up to 16%)of monocytes and granulocytes carrying Fc receptor and OX40 on thei

关 键 词：Karanahan technology OX40 Antitumor immunity Tumor-initiating stem cells Systemic inflammatory reaction 

分 类 号：R730.5[医药卫生—肿瘤]