Abstract
Background and PurposeACT of ex vivo expanded TIL 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 ICB-resistant solid tumors. MethodsPreREP TIL cultures expanded in high dose IL-2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous TCL and/or neoantigens. 6 GMP validations of preREP TIL expansion were performed and TIL cultures from these 6 intermediate products were selected to perform the clinical scale GMP validation of the REP. ResultsTIL expanded in 82% of patient-derived tumor biopsies across different cancer types and these contained tumor- and neoantigen-reactive T cells. During GMP-validations, a variable number of TILs expanded, constituting the intermediate products (preREP). Three finished products (REP) were manufactured 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 TIL 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. ConclusionsNEXTGEN-TIL consists of selected neoantigen-reactive TIL and aims to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TIL.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.