NDLI: Enhanced systemic tumor suppression by in situ vaccine combining radiation and OX40 agonist with CpG therapy

Content Provider	Springer Nature : BioMed Central
Author	Sun, Zhichen Chu, Yanhong Xiao, Jie Yang, Yueling Meng, Fanyan Wang, Xinyue Dong, Yanbing Zhu, Junmeng Wu, Yirong Qin, Lanqun Ke, Yaohua Liu, Baorui Liu, Qin
Abstract	Background In situ tumor vaccine has been gradually becoming a hot research field for its advantage of achieving personalized tumor therapy without prior antigen identification. Various in situ tumor vaccine regimens have been reported to exert considerable antitumor efficacy in preclinical and clinical studies. However, the design of in situ tumor vaccines still needs further optimization and the underlying immune mechanism also waits for deeper investigation. Methods A novel triple in situ vaccine strategy that combining local radiation with intratumoral injection of TLR9 agonist CpG and OX40 agonist was established in this sturdy. Local and abscopal antitumor efficacy as well as survival benefit were evaluated in the bilateral tumors and pulmonary metastasis model of B16F10 melanoma. In situ vaccine-induced immune responses and immune-associated variation in tumor environment were further investigated using multiparameter flow cytometry and RNA sequencing. Base on the analysis, the RT + CpG + αOX40 triple in situ vaccine was combined with checkpoint blockade therapy to explore the potential synergistic antitumor efficacy. Results Enhanced tumor suppression was observed with minimal toxicity in both treated and untreated abscopal tumors after receiving RT + CpG + αOX40 triple vaccine. The introduction of local radiation and OX40 agonist benefit more to the inhibition of local and abscopal lesions respectively, which might be partially attributed to the increase of effector memory T cells in the tumor microenvironment. Further analysis implied that the triple in situ vaccine did not only activate the microenvironment of treated tumors, with the upregulation of multiple immune-associated pathways, but also enhanced systemic antitumor responses, thus achieved superior systemic tumor control and survival benefit. Moreover, the triple in situ vaccine synergized with checkpoint blockade therapy, and significantly improved the therapeutic effect of anti-programmed cell death protein (PD)-1 antibody. Conclusion This triple combining in situ vaccine induced intensive antitumor responses, mediated effective systemic tumor control and survival benefit, and displayed impressive synergistic antitumor effect with checkpoint blockade therapy. These data preliminary confirmed the efficacy, feasibility and safety of the triple combining in situ vaccine, suggesting its great application potential as both monotherapy and a part of combined immunotherapeutic regimens in clinical scenario.
Related Links	https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-04504-w.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	14795876
DOI	10.1186/s12967-023-04504-w
Journal	Journal of Translational Medicine
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2023-09-12
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health TLR9 agonist OX40 agonist Radiation In situ vaccine Tumor microenvironment Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	6.3/2023

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