{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:23:07Z","timestamp":1792002187541,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Iovance Biotherapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance\u2019s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated &gt;1 \u00d7 109 viable TIL cells, with a median yield of 1.1 \u00d7 1010 cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-\u03b3 and TNF-\u03b1 upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC.<\/jats:p>","DOI":"10.3390\/ijms26157151","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T14:11:44Z","timestamp":1753366304000},"page":"7151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Feasibility of Manufacturing and Antitumor Activity of TIL for Advanced Endometrial Cancers"],"prefix":"10.3390","volume":"26","author":[{"given":"Yongliang","family":"Zhang","sequence":"first","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen N.","family":"Moore","sequence":"additional","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir A.","family":"Jazaeri","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Fang","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilabahen","family":"Patel","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Yuhas","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Innamarato","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W.","family":"Dean","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Damirchi","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Yglesias","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongsu","family":"Qi","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle R.","family":"Simpson-Abelson","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Cammaart","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R. R.","family":"Hall","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hequn","family":"Yin","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/S0140-6736(22)00323-3","article-title":"Endometrial cancer","volume":"399","author":"Crosbie","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1056\/NEJMoa2302312","article-title":"Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer","volume":"388","author":"Eskander","year":"2023","journal-title":"N. Engl. J. 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