PMID- 30386680 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 7 IP - 10 DP - 2018 TI - CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy. PG - e1490856 LID - 10.1080/2162402X.2018.1490856 [doi] LID - e1490856 AB - Dendritic cells (DCs) are crucial players in promoting immune responses. Logically, adoptive DC therapy is a promising approach in cancer immunotherapy. One of the major obstacles in cancer immunotherapy in general is the immunosuppressive tumor microenvironment, which hampers the maturation and activation of DCs. Therefore, human clinical outcomes with DC therapy alone have been disappointing. In this study, we use fully serotype 3 oncolytic adenovirus Ad3-hTERT-CMV-hCD40L, expressing human CD40L, to modulate the tumor microenvironment with subsequently improved function of DCs. We evaluated the synergistic effects of Ad3-hTERT-CMV-hCD40L and DCs in the presence of human peripheral blood mononuclear cells ex vivo and in vivo. Tumors treated with Ad3-hTERT-CMV-hCD40L and DCs featured greater antitumor effect compared with unarmed virus or either treatment alone. 100% of humanized mice survived to the end of the experiment, while mice in all other groups died by day 88. Moreover, adenovirally-delivered CD40L induced activation of DCs, leading to induction of Th1 immune responses. These results support clinical trials with Ad3-hTERT-CMV-hCD40L in patients receiving DC therapy. FAU - Zafar, Sadia AU - Zafar S AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. FAU - Sorsa, Suvi AU - Sorsa S AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. FAU - Siurala, Mikko AU - Siurala M AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. FAU - Hemminki, Otto AU - Hemminki O AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - Division of Urology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland. FAU - Havunen, Riikka AU - Havunen R AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. FAU - Cervera-Carrascon, Victor AU - Cervera-Carrascon V AUID- ORCID: 0000-0001-6684-3666 AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. FAU - Santos, Joao Manuel AU - Santos JM AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. FAU - Wang, Hongjie AU - Wang H AD - Department of Pathology, University of Washington, Seattle, WA, USA. FAU - Lieber, Andre AU - Lieber A AD - Department of Pathology, University of Washington, Seattle, WA, USA. FAU - De Gruijl, Tanja AU - De Gruijl T AD - Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. FAU - Kanerva, Anna AU - Kanerva A AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. FAU - Hemminki, Akseli AU - Hemminki A AD - Cancer Gene Therapy Group, University of Helsinki, Helsinki, Finland. AD - TILT Biotherapeutics Ltd, Helsinki, Finland. AD - Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180815 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC6207416 OTO - NOTNLM OT - Ad3 OT - CD40L OT - Dendritic cells OT - T-cells OT - oncolytic adenovirus EDAT- 2018/11/06 06:00 MHDA- 2018/11/06 06:01 PMCR- 2019/08/15 CRDT- 2018/11/03 06:00 PHST- 2018/04/30 00:00 [received] PHST- 2018/06/13 00:00 [revised] PHST- 2018/06/13 00:00 [accepted] PHST- 2018/11/03 06:00 [entrez] PHST- 2018/11/06 06:00 [pubmed] PHST- 2018/11/06 06:01 [medline] PHST- 2019/08/15 00:00 [pmc-release] AID - 1490856 [pii] AID - 10.1080/2162402X.2018.1490856 [doi] PST - epublish SO - Oncoimmunology. 2018 Aug 15;7(10):e1490856. doi: 10.1080/2162402X.2018.1490856. eCollection 2018.