{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:11:01Z","timestamp":1788865861833,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018935","name":"Universit\u00e4tsklinikum Erlangen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018935","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Combination immunotherapy has shown encouraging activity across multiple solid tumors. We report the complete and consecutive cohort of patients with locally advanced oral squamous cell carcinoma (OSCC) treated at a single center within the prospective, multicenter, randomized phase 2 BelieveIT-201 trial (ASND0038), evaluating neoadjuvant intratumoral Toll-like receptor (TLR) 7\/8 agonist (TransCon TLR7\/8 Agonist) therapy combined with systemic immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with non-metastatic OSCC treated within the BelieveIT-201 trial (ASND0038) between April and December 2024 were included. Neoadjuvant therapy comprised two cycles of intratumoral TransCon TLR7\/8 Agonist combined with either intravenous pembrolizumab or TransCon IL-2 \u03b2\/\u03b3 according to 1:1 randomization, followed by surgical resection. The trial was terminated prematurely by the sponsor for reasons unrelated to safety or efficacy, which limited the cohort to six patients. Clinical, radiographic, pathological responses, and safety were assessed. Immunohistochemical analyses of paired pre- and post-treatment tumor samples evaluated immune cell infiltration (CD3, CD8, CD68, CD163). The individual patient was the unit of analysis, and given the small number of patients all analyses are descriptive; no inferential statistical testing was performed. Progression-free survival (PFS) and overall survival (OS) are reported as absolute event counts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six patients were treated (median age 63 years; median follow-up 81 weeks). Three patients achieved a major clinical response, two showed partial response, and one had progressive disease. Pathologic evaluation revealed one complete response, one major response, and four non-responses. All patients underwent surgery; postoperative morbidity was substantial, with at least one grade III adverse event in every patient and one postoperative death. All three patients with a major clinical response developed sterile tumor-associated pseudoabscesses in spatial proximity to the injection site. Immunohistochemical analyses revealed remodeling of the tumor immune microenvironment, including increased T-cell infiltration, most pronounced in the tumor center. Within the first year, two of six patients experienced a progression-free survival event (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091 progressive disease,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091 death). After surgery none of the patients showed disease recurrence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neoadjuvant intratumoral TransCon TLR7\/8 Agonist-based combination immunotherapy was feasible in this small prospective cohort of patients with locally advanced OSCC and was accompanied by consistent remodeling of the tumor immune microenvironment. Because of the limited number of patients and the premature termination of the parent trial, no conclusions on efficacy or on comparative tolerability can be drawn.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00262-026-04515-8","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:23:13Z","timestamp":1788549793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant combined immunotherapy with intratumoral TransCon TLR7\/8 Agonist and systemic TransCon IL-2 \u03b2\/y or pembrolizumab in patients with locally advanced oral cancer\u2014a monocentric experience"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-5977","authenticated-orcid":false,"given":"Manuel","family":"Weber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Trumet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Murk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Alsamra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Backhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Corradini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Kesting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlen","family":"Haderlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"1","key":"4515_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03541-6","volume":"22","author":"W Jiang","year":"2024","unstructured":"Jiang W, Chen L, Li R et al (2024) Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma: a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker. 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M.H.: Consultancy and expert services: Merck Healthcare GmbH; Speaking Fees: Merck HealthCare, MedUpdate, Aurikamed, AstraZeneca; Research funding: German Cancer Aid; Investigator in clinical trials from GSK, AstraZeneca, MSD, Ascendis. M.W.: Consultancy and expert services: Merck Healthcare GmbH, Regeneron GmbH. All other authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The BelieveIT-201 trial (ASND0038, NCT05980598) was approved by the responsible ethics committee and conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent for participation and for the publication of clinical data and images.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"220"}}