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While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1\/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD-1 antibodies on CAR T-cell in treating lung cancer brain metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy, enabling in vivo characterization of red fluorescent tumor cells and CAR T-cell at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis lung carcinoma cells (\n                      <jats:sup>EpCAM\/tdt<\/jats:sup>\n                      LL\/2 cells) were implanted intracranially. Following the formation of brain metastasis, EpCAM-directed CAR T-cell were injected into adjacent brain tissue, and animals received either anti-PD-1 or an isotype control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to controls receiving T-cell lacking a CAR, mice receiving EpCAM-directed CAR T-cell showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD-1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD-1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00262-024-03837-9","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T21:01:16Z","timestamp":1727902876000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis"],"prefix":"10.1007","volume":"73","author":[{"given":"Jens","family":"Blobner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Eberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julika J.","family":"Herold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"M\u00fchlbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina J.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Teske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Karschnia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"van den Heuvel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand","family":"Schallerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellen","family":"Ishikawa-Ankerhold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Thon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg-Christian","family":"Tonn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Subklewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Kobold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick N.","family":"Harter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit R.","family":"Buchholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"von Baumgarten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"3837_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3322\/caac.20102","volume":"61","author":"SS Ramalingam","year":"2011","unstructured":"Ramalingam SS, Owonikoko TK, Khuri FR (2011) Lung cancer: new biological insights and recent therapeutic advances. 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Laura Dengler: No disclosures. Constantin Eberle: No disclosures. Alexander Beck: No disclosures. Julika Herold: No disclosures. Tao Xu: No disclosures. Anton M\u00fchlbauer: No disclosures. Katharina Mueller: No disclosures. Philipp Karschnia: No disclosures. Nico Teske: No disclosures. Dominic van den Heuvel: No disclosures. Ferdinand Schallerer: No disclosures. Hellen Ishikawa-Ankerhold: No disclosures. Marion Subklewe: No disclosures. Niklas Thon: No disclosures. J\u00f6rg-Christian Tonn: Research grants from Novocure and Munich Surgical Imaging; and Royalties from Springer Publisher Intl. Marion Subklewe: No disclosures. Sebastian Kobold: S. K. has received honoraria from TCR2 Inc., Miltenyi, Galapagos, Novartis, BMS, and GSK. S. K. is an inventor of several patents in the field of immuno-oncology. S. K. received license fees from TCR2 Inc. and Carina Biotech. S.K. received research support from TCR2 Inc., Tabby Therapeutics, CatalYm GmBH, Plectonic GmBH, and Arcus Bioscience for work unrelated to the manuscript. Patrick N. Harter: No disclosures. Veit R Buchholz: No disclosures. Louisa von Baumgarten: No disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}],"article-number":"255"}}