{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:42:12Z","timestamp":1789753332331,"version":"4.0.1"},"reference-count":42,"publisher":"Innovative Healthcare Institute","issue":"4","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Enadenotucirev (EnAd) and successor transgene-armed Tumor-Specific Immuno-Gene (T-SIGn) vectors are replication-competent, blood-stable viral vectors that traffic to tumor sites following intravenous (IV) administration. Following initial proof of mechanism for this immunotherapy modality, there is a need to identify a safe dosing approach, understand whether transgenes affect tolerability, and determine how to measure exposure and pharmacodynamic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Safety data from multiple phase 1 trials were aggregated to assess various dosing regimens and toxicities, including those that may be associated with transgene arming. Viral delivery to tumors, peripheral viral persistence, transgene expression, and cytokine responses were also assessed and compared between the unarmed EnAd and armed T-SIGn vectors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IV administration of EnAd and the armed T-SIGn vectors led to virus detection in epithelial tumors and prolonged peripheral virus persistence. Despite the short half-life of the viruses and cell-free nucleic acids, viral DNA or transgene messenger RNA (mRNA) remained detectable in blood at higher dose levels for at least 56 days, indicating sustained release of these molecules likely driven by ongoing viral replication and concomitant transcription of the transgene in tumors. Safety, predominantly defined by the effects of IV administration and associated viremia, was managed by a well-tolerated dosing regimen. To date, no transgene-related or off-target toxicities have been observed. Transient monocyte chemoattractant protein 1 (MCP-1) and interleukin (IL)-6 elevations were associated with viremia. A second phase of elevations of proinflammatory cytokines such as IL-12p70, interferon (IFN) \u03b12, IL-17A, and IFN\u03b3 without clinical symptoms started around day 12, suggesting that release of these cytokines was driven by localized pharmacodynamic effects within the tumor microenvironment (TME).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Armed T-SIGn vectors exhibit the same high tumor selectivity and replicative activity as the unarmed parent EnAd and achieve consistent viral delivery to a broad range of epithelial tumor tissues. The aggregated safety analysis revealed that safety and tolerability are defined by systemic viremia but not off-target or transgene-related toxicities. Nucleic acid and cytokine release from tumors and changes in the TME (e.g., CD8+ T cells), indicative of the mechanism of action of replication-competent viral vectors, constitute potentially valuable data to support the definition of a recommended phase 2 dose and the assessment of the benefit of multicycle administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.36401\/jipo-25-18","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T20:01:01Z","timestamp":1764100861000},"page":"263-275","source":"Crossref","is-referenced-by-count":2,"title":["Replication-Competent, Tumor-Specific Immuno-Gene Vectors Allow for Exchange of Transgenes and Lead to Viral Persistence Following IV Administration"],"prefix":"10.36401","volume":"8","author":[{"given":"Lee S.","family":"Rosen","sequence":"first","affiliation":[{"name":"UCLA Division of Hematology-Oncology, Santa Monica, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ottensmeier","sequence":"additional","affiliation":[{"name":"Liverpool Head and Neck Centre, Institute of Systems, Molecular and Integrative Biology, University of Liverpool & Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hawkins","sequence":"additional","affiliation":[{"name":"University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aung","family":"Naing","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guru","family":"Sonpavde","sequence":"additional","affiliation":[{"name":"AdventHealth Cancer Institute, Orlando, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Van Tine","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen E.","family":"Parkes","sequence":"additional","affiliation":[{"name":"Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Headington, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"O\u2019Cathail","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Ru","family":"Ji","sequence":"additional","affiliation":[{"name":"Akamis Bio Inc, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Thomas","sequence":"additional","affiliation":[{"name":"Akamis Bio Ltd., Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Stacey","sequence":"additional","affiliation":[{"name":"Akamis Bio Ltd., Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Stella","family":"Sasso","sequence":"additional","affiliation":[{"name":"Akamis Bio Ltd., Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-3143","authenticated-orcid":true,"given":"Oliver","family":"Rosen","sequence":"additional","affiliation":[{"name":"Akamis Bio Inc, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22027","reference":[{"key":"i2590-017X-8-4-263-b01","series-title":"Science","first-page":"854","article-title":"Experimental therapy of human glioma by means of a genetically engineered virus mutant","volume":"252","author":"Martuza","year":"1991","unstructured":"Martuza RL,\nMalick A,\nMarkert JM, et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991;252:854\u2013856."},{"key":"i2590-017X-8-4-263-b02","series-title":"Cancer Sci","first-page":"1373","article-title":"Oncolytic virus therapy: a new era of cancer treatment at dawn","volume":"107","author":"Fukuhara","year":"2016","unstructured":"Fukuhara H,\nIno Y,\nTodo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 2016;107:1373\u20131379."},{"key":"i2590-017X-8-4-263-b03","series-title":"Nat Rev Clin Oncol","first-page":"558","article-title":"Intratumoural administration and tumour tissue targeting of cancer immunotherapies","volume":"18","author":"Melero","year":"2021","unstructured":"Melero I,\nCastanon E,\nAlvarez M, et al. Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Nat Rev Clin Oncol. 2021;18:558\u2013576."},{"key":"i2590-017X-8-4-263-b04","series-title":"Clin Cancer Res","first-page":"2555","article-title":"A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization","volume":"12","author":"Laurie","year":"2006","unstructured":"Laurie SA,\nBell JC,\nAtkins HL, et al. A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin Cancer Res. 2006;12:2555\u20132562."},{"key":"i2590-017X-8-4-263-b05","series-title":"Cancers (Basel)","first-page":"160","article-title":"A phase II study of pelareorep (REOLYSIN\u00ae) in combination with gemcitabine for patients with advanced pancreatic adenocarcinoma","volume":"10","author":"Mahalingam","year":"2018","unstructured":"Mahalingam D,\nGoel S,\nAparo S, et al. A phase II study of pelareorep (REOLYSIN\u00ae) in combination with gemcitabine for patients with advanced pancreatic adenocarcinoma. Cancers (Basel). 2018;10:160."},{"key":"i2590-017X-8-4-263-b06","series-title":"Nat Rev Clin Oncol","first-page":"160","article-title":"Therapy with oncolytic viruses: progress and challenges","volume":"20","author":"Shalhout","year":"2023","unstructured":"Shalhout SZ,\nMiller DM,\nEmerick KS,\nKaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20:160\u2013177."},{"key":"i2590-017X-8-4-263-b07","series-title":"PLoS One","first-page":"e0177810","article-title":"Development of a versatile oncolytic virus platform for local intra-tumoral expression of therapeutic transgenes","volume":"12","author":"Marino","year":"2017","unstructured":"Marino N,\nIllingworth S,\nKodialbail P, et al. Development of a versatile oncolytic virus platform for local intra-tumoral expression of therapeutic transgenes. PLoS One. 2017;12:e0177810."},{"key":"i2590-017X-8-4-263-b08","series-title":"J Immunother Cancer","first-page":"71","article-title":"Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection","volume":"5","author":"Garcia-Carbonero","year":"2017","unstructured":"Garcia-Carbonero R,\nSalazar R,\nDuran I, et al. Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. J Immunother Cancer. 2017;5:71."},{"key":"i2590-017X-8-4-263-b09","series-title":"J Immunother Cancer","first-page":"e010016","article-title":"First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments","volume":"12","author":"Naing","year":"2024","unstructured":"Naing A,\nKhalil D,\nRosen O, et al. First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. J Immunother Cancer. 2024;12:e010016."},{"key":"i2590-017X-8-4-263-b10","series-title":"PLoS One","first-page":"e2409","article-title":"Directed evolution generates a novel oncolytic virus for the treatment of colon cancer","volume":"3","author":"Kuhn","year":"2008","unstructured":"Kuhn I,\nHarden P,\nBauzon M, et al. Directed evolution generates a novel oncolytic virus for the treatment of colon cancer. PLoS One. 2008;3:e2409."},{"key":"i2590-017X-8-4-263-b11","series-title":"Nat Rev Cancer","first-page":"698","article-title":"Context-dependent roles of complement in cancer","volume":"19","author":"Roumenina","year":"2019","unstructured":"Roumenina LT,\nDaugan MV,\nPetitprez F, et al. Context-dependent roles of complement in cancer. Nat Rev Cancer. 2019;19:698\u2013715."},{"key":"i2590-017X-8-4-263-b12","series-title":"J Immunother Cancer","first-page":"20","article-title":"A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)","volume":"7","author":"Machiels","year":"2019","unstructured":"Machiels JP,\nSalazar R,\nRottey S, et al. A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J Immunother Cancer. 2019;7:20."},{"key":"i2590-017X-8-4-263-b13","series-title":"J Immunother Cancer","first-page":"e006561","article-title":"Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced\/metastatic epithelial cancer: a phase I clinical trial (SPICE)","volume":"11","author":"Fakih","year":"2023","unstructured":"Fakih M,\nHarb W,\nMahadevan D, et al. Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced\/metastatic epithelial cancer: a phase I clinical trial (SPICE). J Immunother Cancer. 2023;11:e006561."},{"key":"i2590-017X-8-4-263-b14","series-title":"Radiat Oncol","first-page":"151","article-title":"A phase 1 trial of the safety, tolerability and biological effects of intravenous enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)","volume":"15","author":"O\u2019Cathail","year":"2020","unstructured":"O\u2019Cathail SM,\nDavis S,\nHolmes J, et al. A phase 1 trial of the safety, tolerability and biological effects of intravenous enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR). Radiat Oncol. 2020;15:151."},{"key":"i2590-017X-8-4-263-b15","series-title":"Cancers (Basel)","first-page":"1302","article-title":"Agonistic CD40 antibodies in cancer treatment","volume":"13","author":"Djureinovic","year":"2021","unstructured":"Djureinovic D,\nWang M,\nKluger HM. Agonistic CD40 antibodies in cancer treatment. Cancers (Basel). 2021;13:1302."},{"key":"i2590-017X-8-4-263-b16","series-title":"Front Immunol","first-page":"940674","article-title":"Next generation CD40 agonistic antibodies for cancer immunotherapy","volume":"13","author":"Salomon","year":"2022","unstructured":"Salomon R,\nDahan R. Next generation CD40 agonistic antibodies for cancer immunotherapy. Front Immunol. 2022;13:940674."},{"key":"i2590-017X-8-4-263-b17","series-title":"Invest New Drugs","first-page":"317","article-title":"A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies","volume":"41","author":"Khalil","year":"2023","unstructured":"Khalil DN,\nPrieto Gonz\u00e1lez-Albo I,\nRosen L, et al. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023;41:317\u2013323."},{"key":"i2590-017X-8-4-263-b18","series-title":"Signal Transduct Target Ther","first-page":"145","article-title":"Exosomes: key players in cancer and potential therapeutic strategy","volume":"5","author":"Dai","year":"2020","unstructured":"Dai J,\nSu Y,\nZhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. 2020;5:145."},{"key":"i2590-017X-8-4-263-b19","series-title":"Mol Cancer","first-page":"15","article-title":"Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance","volume":"22","author":"Stejskal","year":"2023","unstructured":"Stejskal P,\nGoodarzi H,\nSrovnal J, et al. Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance. Mol Cancer. 2023;22:15."},{"key":"i2590-017X-8-4-263-b20","series-title":"Cytokine Growth Factor Rev","first-page":"155","article-title":"Interleukin-12 in anti-tumor immunity and immunotherapy","volume":"13","author":"Colombo","year":"2002","unstructured":"Colombo MP,\nTrinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 2002;13:155\u2013168."},{"key":"i2590-017X-8-4-263-b21","series-title":"J Clin Oncol","first-page":"528","article-title":"Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma","volume":"41","author":"Chesney","year":"2022","unstructured":"Chesney JA,\nRibas A,\nLong GV, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. J Clin Oncol. 2022;41:528\u2013540."},{"key":"i2590-017X-8-4-263-b01","series-title":"Science","first-page":"854","article-title":"Experimental therapy of human glioma by means of a genetically engineered virus mutant","volume":"252","author":"Martuza","year":"1991","unstructured":"Martuza RL,\nMalick A,\nMarkert JM, et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991;252:854\u2013856."},{"key":"i2590-017X-8-4-263-b02","series-title":"Cancer Sci","first-page":"1373","article-title":"Oncolytic virus therapy: a new era of cancer treatment at dawn","volume":"107","author":"Fukuhara","year":"2016","unstructured":"Fukuhara H,\nIno Y,\nTodo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 2016;107:1373\u20131379."},{"key":"i2590-017X-8-4-263-b03","series-title":"Nat Rev Clin Oncol","first-page":"558","article-title":"Intratumoural administration and tumour tissue targeting of cancer immunotherapies","volume":"18","author":"Melero","year":"2021","unstructured":"Melero I,\nCastanon E,\nAlvarez M, et al. Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Nat Rev Clin Oncol. 2021;18:558\u2013576."},{"key":"i2590-017X-8-4-263-b04","series-title":"Clin Cancer Res","first-page":"2555","article-title":"A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization","volume":"12","author":"Laurie","year":"2006","unstructured":"Laurie SA,\nBell JC,\nAtkins HL, et al. A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin Cancer Res. 2006;12:2555\u20132562."},{"key":"i2590-017X-8-4-263-b05","series-title":"Cancers (Basel)","first-page":"160","article-title":"A phase II study of pelareorep (REOLYSIN\u00ae) in combination with gemcitabine for patients with advanced pancreatic adenocarcinoma","volume":"10","author":"Mahalingam","year":"2018","unstructured":"Mahalingam D,\nGoel S,\nAparo S, et al. A phase II study of pelareorep (REOLYSIN\u00ae) in combination with gemcitabine for patients with advanced pancreatic adenocarcinoma. Cancers (Basel). 2018;10:160."},{"key":"i2590-017X-8-4-263-b06","series-title":"Nat Rev Clin Oncol","first-page":"160","article-title":"Therapy with oncolytic viruses: progress and challenges","volume":"20","author":"Shalhout","year":"2023","unstructured":"Shalhout SZ,\nMiller DM,\nEmerick KS,\nKaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20:160\u2013177."},{"key":"i2590-017X-8-4-263-b07","series-title":"PLoS One","first-page":"e0177810","article-title":"Development of a versatile oncolytic virus platform for local intra-tumoral expression of therapeutic transgenes","volume":"12","author":"Marino","year":"2017","unstructured":"Marino N,\nIllingworth S,\nKodialbail P, et al. Development of a versatile oncolytic virus platform for local intra-tumoral expression of therapeutic transgenes. PLoS One. 2017;12:e0177810."},{"key":"i2590-017X-8-4-263-b08","series-title":"J Immunother Cancer","first-page":"71","article-title":"Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection","volume":"5","author":"Garcia-Carbonero","year":"2017","unstructured":"Garcia-Carbonero R,\nSalazar R,\nDuran I, et al. Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. J Immunother Cancer. 2017;5:71."},{"key":"i2590-017X-8-4-263-b09","series-title":"J Immunother Cancer","first-page":"e010016","article-title":"First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments","volume":"12","author":"Naing","year":"2024","unstructured":"Naing A,\nKhalil D,\nRosen O, et al. First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. J Immunother Cancer. 2024;12:e010016."},{"key":"i2590-017X-8-4-263-b10","series-title":"PLoS One","first-page":"e2409","article-title":"Directed evolution generates a novel oncolytic virus for the treatment of colon cancer","volume":"3","author":"Kuhn","year":"2008","unstructured":"Kuhn I,\nHarden P,\nBauzon M, et al. Directed evolution generates a novel oncolytic virus for the treatment of colon cancer. PLoS One. 2008;3:e2409."},{"key":"i2590-017X-8-4-263-b11","series-title":"Nat Rev Cancer","first-page":"698","article-title":"Context-dependent roles of complement in cancer","volume":"19","author":"Roumenina","year":"2019","unstructured":"Roumenina LT,\nDaugan MV,\nPetitprez F, et al. Context-dependent roles of complement in cancer. Nat Rev Cancer. 2019;19:698\u2013715."},{"key":"i2590-017X-8-4-263-b12","series-title":"J Immunother Cancer","first-page":"20","article-title":"A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)","volume":"7","author":"Machiels","year":"2019","unstructured":"Machiels JP,\nSalazar R,\nRottey S, et al. A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J Immunother Cancer. 2019;7:20."},{"key":"i2590-017X-8-4-263-b13","series-title":"J Immunother Cancer","first-page":"e006561","article-title":"Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced\/metastatic epithelial cancer: a phase I clinical trial (SPICE)","volume":"11","author":"Fakih","year":"2023","unstructured":"Fakih M,\nHarb W,\nMahadevan D, et al. Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced\/metastatic epithelial cancer: a phase I clinical trial (SPICE). J Immunother Cancer. 2023;11:e006561."},{"key":"i2590-017X-8-4-263-b14","series-title":"Radiat Oncol","first-page":"151","article-title":"A phase 1 trial of the safety, tolerability and biological effects of intravenous enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)","volume":"15","author":"O\u2019Cathail","year":"2020","unstructured":"O\u2019Cathail SM,\nDavis S,\nHolmes J, et al. A phase 1 trial of the safety, tolerability and biological effects of intravenous enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR). Radiat Oncol. 2020;15:151."},{"key":"i2590-017X-8-4-263-b15","series-title":"Cancers (Basel)","first-page":"1302","article-title":"Agonistic CD40 antibodies in cancer treatment","volume":"13","author":"Djureinovic","year":"2021","unstructured":"Djureinovic D,\nWang M,\nKluger HM. Agonistic CD40 antibodies in cancer treatment. Cancers (Basel). 2021;13:1302."},{"key":"i2590-017X-8-4-263-b16","series-title":"Front Immunol","first-page":"940674","article-title":"Next generation CD40 agonistic antibodies for cancer immunotherapy","volume":"13","author":"Salomon","year":"2022","unstructured":"Salomon R,\nDahan R. Next generation CD40 agonistic antibodies for cancer immunotherapy. Front Immunol. 2022;13:940674."},{"key":"i2590-017X-8-4-263-b17","series-title":"Invest New Drugs","first-page":"317","article-title":"A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies","volume":"41","author":"Khalil","year":"2023","unstructured":"Khalil DN,\nPrieto Gonz\u00e1lez-Albo I,\nRosen L, et al. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023;41:317\u2013323."},{"key":"i2590-017X-8-4-263-b18","series-title":"Signal Transduct Target Ther","first-page":"145","article-title":"Exosomes: key players in cancer and potential therapeutic strategy","volume":"5","author":"Dai","year":"2020","unstructured":"Dai J,\nSu Y,\nZhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. 2020;5:145."},{"key":"i2590-017X-8-4-263-b19","series-title":"Mol Cancer","first-page":"15","article-title":"Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance","volume":"22","author":"Stejskal","year":"2023","unstructured":"Stejskal P,\nGoodarzi H,\nSrovnal J, et al. Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance. Mol Cancer. 2023;22:15."},{"key":"i2590-017X-8-4-263-b20","series-title":"Cytokine Growth Factor Rev","first-page":"155","article-title":"Interleukin-12 in anti-tumor immunity and immunotherapy","volume":"13","author":"Colombo","year":"2002","unstructured":"Colombo MP,\nTrinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 2002;13:155\u2013168."},{"key":"i2590-017X-8-4-263-b21","series-title":"J Clin Oncol","first-page":"528","article-title":"Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma","volume":"41","author":"Chesney","year":"2022","unstructured":"Chesney JA,\nRibas A,\nLong GV, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. 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