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Immuno-oncology technology | Free PMC Article

BACKGROUND: Adoptive cell therapy (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 28%-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on ex vivo neoantigen recognition, in patients with advanced epithelial tumors and immune checkpoint blockade (ICB)-resistant solid tumors. MATERIALS AND METHODS: Pre-rapid expansion protocol (REP) TIL cultures expanded in high-dose interleukin 2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous tumor cell lines (TCLs) and/or neoantigens. Six good manufacturing practice (GMP)-grade validations of pre-REP TIL expansion were carried out and TIL cultures from these six intermediate products were selected to carry out the clinical-scale GMP validation of the REP. RESULTS: TILs expanded in 82% of patient-derived tumor biopsies across different cancer types and these frequently contained tumor- and neoantigen-reactive T cells. During GMP validations, a variable number of TIL cultures expanded, constituting the intermediate products (pre-REP). Three finished products were manufactured using a REP which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TILs from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2. CONCLUSIONS: NEXTGEN-TIL exploits ex vivo expanded neoantigen-reactive TIL to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TILs.

Author Info: (1) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (2) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d

Author Info: (1) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (2) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (3) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (4) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (5) Banc de Sang i Teixits (Blood and Tissue Bank, BST), Barcelona, Spain. (6) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (7) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (8) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (9) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (10) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (11) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (12) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (13) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (14) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (15) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (16) Surgery Branch, National Cancer Institute, Bethesda, USA. (17) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (18) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (19) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (20) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (21) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (22) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (23) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (24) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (25) Hematology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (26) Banc de Sang i Teixits (Blood and Tissue Bank, BST), Barcelona, Spain. Vall d'Hebron Research Institute-Autonomous University of Barcelona (VHIR-UAB), Barcelona. (27) Banc de Sang i Teixits (Blood and Tissue Bank, BST), Barcelona, Spain. (28) Banc de Sang i Teixits (Blood and Tissue Bank, BST), Barcelona, Spain. (29) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. (30) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona. Institute of Oncology (IOB)-Quir—n, Barcelona-Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic-CIBER en oncolog’a (CIBERONC) ISCIII, Madrid. (31) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. Department of Basic Medical Sciences, Faculty of Medicine, University of Sant Pablo-CEU, CEU Universities, Madrid, Spain. (32) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona. (33) Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona.

Citation: Immunooncol Technol 2025 Mar 25:101030 Epub12/02/2024

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/39911162

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