{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:11:00Z","timestamp":1789593060692,"version":"build-2803163510"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Engineered viral vectors represent a promising strategy to trigger antigen-specific antitumor T cell responses. Arenaviruses have been widely studied because of their ability to elicit potent and protective T cell responses. Here, we provide an overview of a novel intravenously administered, replication-competent, non-lytic arenavirus-based vector technology that delivers tumor antigens to induce antigen-specific anti-cancer T cell responses. Preclinical studies in mice and cell culture experiments with human peripheral blood mononuclear cells demonstrate that arenavirus vectors preferentially infect antigen-presenting cells. This, in conjunction with a non-lytic functional activation of the infected antigen-presenting cells, leads to a robust antigen-specific CD8<jats:sup>+<\/jats:sup> T cell response. T cell migration to, and infiltration of, the tumor microenvironment has been demonstrated in various preclinical tumor models with vectors encoding self- and non\u2013self-antigens. The available data also suggest that arenavirus\u2013based vector therapy can induce immunological memory protecting from tumor rechallenge. Based on promising preclinical data, a phase 1\/2 clinical trial was initiated and is currently ongoing to test the activity and safety of arenavirus vectors, HB-201 and HB-202, created using lymphocytic choriomeningitis virus and Pichinde virus, respectively. Both vectors have been engineered to deliver non-oncogenic versions of the human papilloma virus 16 (HPV16) antigens E7 and E6 and will be injected intravenously with or without an initial intratumoral dose. This dose escalation\/expansion study is being conducted in patients with recurrent or metastatic HPV16+ cancers. Promising preliminary data from this ongoing clinical study have been reported. Immunogenicity data from several patients demonstrate that a single injection of HB-201 or HB-202 monotherapy is highly immunogenic, as evidenced by an increase in inflammatory cytokines\/chemokines and the expansion of antigen-specific CD8<jats:sup>+<\/jats:sup> T cell responses. This response can be further enhanced by alternating injections of HB-202 and HB-201, which has resulted in frequencies of circulating HPV16 E7\/E6-specific CD8<jats:sup>+<\/jats:sup> T cells of up to 40% of the total CD8<jats:sup>+<\/jats:sup> T cell compartment in peripheral blood in analyses to date. Treatment with intravenous administration also resulted in a disease control rate of 73% among 11 evaluable patients with head and neck cancer dosed every three weeks, including 2 patients with a partial response.<\/jats:p>","DOI":"10.3389\/fonc.2021.732166","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T05:40:56Z","timestamp":1634190056000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Development and Characterization of a Novel Non-Lytic Cancer Immunotherapy Using a Recombinant Arenavirus Vector Platform"],"prefix":"10.3389","volume":"11","author":[{"given":"Henning","family":"Lauterbach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kia","family":"Katchar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Iacobucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Schlienger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Berka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josipa","family":"Raguz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ahmadi-Erber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Schippers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Stemeseder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Pinschewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Matushansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus K.","family":"Orlinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4161\/21645515.2014.973317","article-title":"Antigen-Specific Vaccines for Cancer Treatment","volume":"10","author":"Tagliamonte","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2020.101430","article-title":"New Viral Vectors for Infectious Diseases and Cancer","volume":"50","author":"Sasso","year":"2020","journal-title":"Semin Immunol"},{"key":"B3","unstructured":"A Study of TheraT\u00ae Vector(s) Expressing HPV 16+ in Patients With HPV 16+ Confirmed Cancers (Nct04180215)2020"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100209","article-title":"Heterologous Arenavirus Vector Prime-Boost Overrules Self-Tolerance for Efficient Tumor-Specific CD8 T Cell Attack","volume":"2","author":"Bonilla","year":"2021","journal-title":"Cell Rep Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15327","article-title":"Replicating Viral Vector Platform Exploits Alarmin Signals for Potent CD8(+) T Cell-Mediated Tumour Immunotherapy","volume":"8","author":"Kallert","year":"2017","journal-title":"Nat Commun"},{"key":"B6","volume-title":"Fields Virology","author":"Knipe","year":"2013"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-642-56055-2_1","article-title":"Lymphocytic Choriomeningitis Virus and Immunology","volume":"263","author":"Zinkernagel","year":"2002","journal-title":"Curr Top Microbiol Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"V","DOI":"10.1007\/978-3-642-56055-2","article-title":"Arenaviruses. 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