{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T20:06:38Z","timestamp":1783800398422,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017242","name":"National Institutes for Food and Drug Control","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chimeric antigen receptor (CAR) T cells show limited efficacy in solid tumors. Oncolytic viruses (OVs), especially those expressing immunomodulatory cytokines like interleukin-12 (IL-12), potentiate to synergize with CAR-T therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated an IL-12-expressing oncolytic herpes simplex virus type 2 (oHSV-2-IL-12) with mesothelin-targeting SS1-ICOSBBZ-CAR-T to treat Capan-2 pancreatic cancer cells xenografts in B-NDG immunodeficient mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SS1-ICOSBBZ-CAR-T alone exhibited partial anti-tumor activity, but could not eradicate established tumors. Intra-tumoral oHSV-2-IL-12 administration potently enhanced CAR-T efficacy, achieving complete and durable tumor elimination even at reduced CAR-T doses. After the initial tumors were fully eliminated by combination therapy, mice were re-challenged by inoculating mesothelin-negative and mesothelin-positive tumor cell lines on the left and right flanks, respectively. In the combination treatment group, mesothelin-positive tumors failed to form new tumors within two weeks after re-challenge, whereas mesothelin-negative tumors grew normally. These findings indicate that oHSV-2-IL-12 combined with CAR-T therapy confers durable, antigen-specific protection against tumor re-challenge. Mechanistically, oHSV-2-IL-12 promoted CAR-T proliferation and persistence in peripheral blood and spleen. IL-12 expression also augmented the direct oncolytic effect of oHSV-2 in immunodeficient hosts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This synergistic approach achieves durable potent tumor clearance with reduced CAR-T doses, offering a transformative strategy against pancreatic cancer and other challenging solid malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1664289","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:07:18Z","timestamp":1768547238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IL-12-armed oncolytic HSV-2 enhances CAR T cell efficacy against pancreatic cancer in xenografted models"],"prefix":"10.3389","volume":"16","author":[{"given":"Chongfeng","family":"Xu","sequence":"first","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]},{"name":"State Key Laboratory of Drug Regulatory Science","place":["Beijing, China"]},{"name":"Beijing Key Laboratory of Quality Control and Non-clinical Research and Evaluation for Cellular and Gene Therapy Medicinal Products","place":["Beijing, China"]},{"name":"Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Zhou","sequence":"additional","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liang","sequence":"additional","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoya","family":"Li","sequence":"additional","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]},{"name":"State Key Laboratory of Drug Regulatory Science","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Zhucheng People\u2019s Hospital","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiying","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyi","family":"Tu","sequence":"additional","affiliation":[{"name":"Cell Collection and Research Center, Institute of Biological Products, National Institutes for Food and Drug Control (NIFDC)","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binlei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hubei University of Technology","place":["Wuhan, China"]},{"name":"Wuhan Binhui Biotechnology Co. 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