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However, there are some drawbacks to this therapy, such as toxicity, short half-life in the serum, and immunosuppressive tumor microenvironment that could limit the use of CD19BiTEs in the clinic. Here, we generate an oncolytic vaccinia virus (OVV) encoding a CD19-specific BiTE (OVV-CD19BiTE). We demonstrate that OVV-CD19BiTE\u2019s ability to replicate and induce oncolysis was similar to that of its parental counterpart. Supernatants from OVV-CD19BiTE-infected cells could induce activation and proliferation of human T cells, and the bystander effect of the virus was also demonstrated. In vivo study showed that OVV-CD19BiTE selectively replicated within tumor tissue, and contributed to a more significantly increased percentage of CD3, CD8, and na\u00efve CD8 T subpopulations within tumors in contrast to blinatumomab. More importantly, treatment with OVV-CD19BiTE both in vitro and in vivo resulted in potent antitumor activity in comparison with control OVV or blinatumomab, a first-in-class BiTE, thereby resulting in long-term tumor remissions without relapse. The study provides strong evidence for the therapeutic benefits of CD19-targeting BiTE expression by OVV, and suggests the feasibility of testing the approach in clinical trials.<\/jats:p>","DOI":"10.1038\/s41408-022-00634-4","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:02:49Z","timestamp":1646038969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["CD19-targeted BiTE expression by an oncolytic vaccinia virus significantly augments therapeutic efficacy against B-cell lymphoma"],"prefix":"10.1038","volume":"12","author":[{"given":"Wen","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7772-220X","authenticated-orcid":false,"given":"Shibing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-6674","authenticated-orcid":false,"given":"Wenbin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"634_CR1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1001\/jamaoncol.2019.3869","volume":"6","author":"FL Locke","year":"2020","unstructured":"Locke FL, Go WY, Neelapu SS. Development and use of the anti-CD19 chimeric antigen receptor T-cell therapy axicabtagene ciloleucel in large B-cell lymphoma: a review. JAMA Oncol. 2020;6:281\u201390.","journal-title":"JAMA Oncol"},{"key":"634_CR2","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1172\/JCI129208","volume":"130","author":"MJ Frigault","year":"2020","unstructured":"Frigault MJ, Maus MV. State of the art in CAR T cell therapy for CD19+ B cell malignancies. J Clin Invest. 2020;130:1586\u201394.","journal-title":"J Clin Invest"},{"key":"634_CR3","doi-asserted-by":"publisher","first-page":"e0141669","DOI":"10.1371\/journal.pone.0141669","volume":"10","author":"W Deisting","year":"2015","unstructured":"Deisting W, Raum T, Kufer P, Baeuerle PA, Munz M. Impact of diverse immune evasion mechanisms of cancer cells on T cells engaged by EpCAM\/CD3-bispecific antibody construct AMG 110. PLoS ONE. 2015;10:e0141669.","journal-title":"PLoS ONE"},{"key":"634_CR4","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41573-019-0028-1","volume":"18","author":"AF Labrijn","year":"2019","unstructured":"Labrijn AF, Janmaat ML, Reichert JM, Parren P. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18:585\u2013608.","journal-title":"Nat Rev Drug Discov"},{"key":"634_CR5","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1056\/NEJMoa1609783","volume":"376","author":"H Kantarjian","year":"2017","unstructured":"Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836\u201347.","journal-title":"N Engl J Med"},{"key":"634_CR6","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1007\/s00277-020-04221-0","volume":"99","author":"A Viardot","year":"2020","unstructured":"Viardot A, Locatelli F, Stieglmaier J, Zaman F, Jabbour E. Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies. Ann Hematol. 2020;99:2215\u201329.","journal-title":"Ann Hematol"},{"key":"634_CR7","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1080\/17474086.2019.1676717","volume":"12","author":"A Bukhari","year":"2019","unstructured":"Bukhari A, Lee ST. Blinatumomab: a novel therapy for the treatment of non-Hodgkin\u2019s lymphoma. 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The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35"}}