Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression
Name:
35845722.pdf
Size:
3.356Mb
Format:
PDF
Description:
Identified with Open Access button
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.
Affiliation
Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandIssue Date
2022
Metadata
Show full item recordAbstract
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
OncoimmunologyDOI
10.1080/2162402x.2022.2096572PubMed ID
35845722Additional Links
https://dx.doi.org/10.1080/2162402x.2022.2096572Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1080/2162402x.2022.2096572
Scopus Count
Collections
Related articles
- Oncolytic adenovirus shapes the ovarian tumor microenvironment for potent tumor-infiltrating lymphocyte tumor reactivity.
- Authors: Santos JM, Heiniö C, Cervera-Carrascon V, Quixabeira DCA, Siurala M, Havunen R, Butzow R, Zafar S, de Gruijl T, Lassus H, Kanerva A, Hemminki A
- Issue date: 2020 Jan
- Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma.
- Authors: Huang J, Zheng M, Zhang Z, Tang X, Chen Y, Peng A, Peng X, Tong A, Zhou L
- Issue date: 2021 Sep
- Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control.
- Authors: Quixabeira DCA, Zafar S, Santos JM, Cervera-Carrascon V, Havunen R, Kudling TV, Basnet S, Anttila M, Kanerva A, Hemminki A
- Issue date: 2021
- Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers.
- Authors: Santos J, Heiniö C, Quixabeira D, Zafar S, Clubb J, Pakola S, Cervera-Carrascon V, Havunen R, Kanerva A, Hemminki A
- Issue date: 2021 Apr 22
- An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage.
- Authors: Pakola S, Quixabeira DCA, Kudling TV, Clubb JHA, Grönberg-Vähä-Koskela S, Basnet S, Jirovec E, Arias V, Haybout L, Heiniö C, Santos JM, Cervera-Carrascon V, Havunen R, Anttila M, Hemminki A
- Issue date: 2023