uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus
University of Helsinki.
University of Helsinki.
University of Helsinki.
University of Helsinki.
Show others and affiliations
2012 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 72, no 9, 2327-2338 p.Article in journal (Refereed) Published
Abstract [en]

Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (TH1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)–mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the TH1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of TH1 cytokines.

Place, publisher, year, edition, pages
2012. Vol. 72, no 9, 2327-2338 p.
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-175759DOI: 10.1158/0008-5472.CAN-11-2975ISI: 000307345300019PubMedID: 22396493OAI: oai:DiVA.org:uu-175759DiVA: diva2:532931
Available from: 2012-06-12 Created: 2012-06-12 Last updated: 2012-10-02Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Loskog, Angelica S I
By organisation
Clinical Immunology
In the same journal
Cancer Research
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 260 hits
ReferencesLink to record
Permanent link

Direct link