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    Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression

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    Authors
    Kudling, T. V.
    Clubb, J. H. A.
    Quixabeira, D. C. A.
    Santos, J. M.
    Havunen, R.
    Kononov, Alexander
    Heiniö, C.
    Cervera-Carrascon, V.
    Pakola, S.
    Basnet, S.
    Grönberg-Vähä-Koskela, S.
    Arias, V.
    Gladwyn-Ng, I.
    Aro, K.
    Bäck, L.
    Räsänen, J.
    Ilonen, I.
    Borenius, K.
    Räsänen, M.
    Hemminki, O.
    Rannikko, A.
    Kanerva, A.
    Tapper, J.
    Hemminki, A.
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    Affiliation
    Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
    Issue Date
    2022
    
    Metadata
    Show full item record
    Abstract
    Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead to a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, in part due to a low concentration of the cytokine within the tumor. We hypothesized that arming an oncolytic adenovirus with Interleukin 7, enabling high expression localized to the tumor microenvironment, would overcome systemic delivery issues and improve therapeutic efficacy. We evaluated the effects of Ad5/3-E2F-d24-hIL7 (TILT-517) on tumor growth, immune cell activation and cytokine profiles in the tumor microenvironment using three clinically relevant animal models and ex vivo tumor cultures. Our data showed that local treatment of tumor bearing animals with Ad5/3- E2F-d24-hIL7 significantly decreased cancer growth and increased frequency of tumor-infiltrating cells. Ad5/3-E2F-d24-hIL7 promoted notable upregulation of pro-inflammatory cytokines, and concomitant activation and migration of CD4+ and CD8 + T cells. Interleukin 7 expression within the tumor was positively correlated with increased number of cytotoxic CD4+ cells and IFNg-producing CD4+ and CD8+ cells. These findings offer an approach to overcome the current limitations of conventional IL7 therapy and could therefore be translated to the clinic.
    Citation
    Kudling TV, Clubb JHA, Quixabeira DCA, Santos JM, Havunen R, Kononov A, et al. Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression. Oncoimmunology. 2022;11(1):2096572. PubMed PMID: 35845722. Pubmed Central PMCID: PMC9278414. Epub 2022/07/19. eng.
    Journal
    Oncoimmunology
    URI
    http://hdl.handle.net/10541/625437
    DOI
    10.1080/2162402x.2022.2096572
    PubMed ID
    35845722
    Additional Links
    https://dx.doi.org/10.1080/2162402x.2022.2096572
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1080/2162402x.2022.2096572
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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