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In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti\u2010CD3scfv within the tumor site strictly, which depended on the E1A\u2010engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane\u2010bound anti\u2010CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti\u2010CD3scfv gene driven by human \u03b1\u2010fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti\u2010CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively <jats:italic>in vitro<\/jats:italic>. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging <jats:italic>in vitro<\/jats:italic> 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co\u2010transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5\u2010fluorouracil (5\u2010FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. In summary, this study provides a promising strategy for solid tumor immunotherapy.<\/jats:p>","DOI":"10.1002\/ijc.30846","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T08:35:10Z","timestamp":1498206910000},"page":"1445-1457","source":"Crossref","is-referenced-by-count":10,"title":["Surface expression of anti\u2010CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A\u2010engineered human umbilical cord mesenchymal stem cells"],"prefix":"10.1002","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-5743","authenticated-orcid":false,"given":"Qing","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology Department of Pharmacy, Institute of Hematology &amp; Hospital of Blood Diseases, Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin 300020 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