NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy
Abstract
Abstract Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct ACT approach, where T cell responses against personalized neoantigens are systematically generated from autologous peripheral blood. Here we report the establishment of NEO-STIM, an ex vivo induction process to prime and expand pre-existing memory and de novo CD8 + and CD4 + T cell responses, thereby highlighting critical parameters for generating potent neoantigen-specific T cell responses. The drug products comprise mutant-reactive, polyfunctional, and cytotoxic CD8 + and CD4 + T cells, able to recognize autologous tumor material. Following infusion, T cell responses are detected in tumor and blood of a patient, and display activated/exhausted and cytotoxic phenotypes. A first-in-human clinical trial (NCT04625205) recently further validated proof-of-concept, supporting continued development of this ACT approach.
Article Details
Authors (39)
Divya Lenkala
Jessica Kohler
Brian McCarthy
Michael Nelson
Noor A. M. Bakker
Renate de Boer
Emily K. Jackson
Joong Hyuk F. Sheen
Susan Hannes
Ekaterina Esaulova
Kai Stewart
Claudia Gottstein
John Attanasio
Flavian D. Brown
Sebastian Hymson
Shirisha Meda
Maaike van Zon
Saskia Scheij
Rhianne Voogd
Brenda Raud
Ziyan Xu
Department of Molecular Genetics and Microbiology, Duke University Medical Center
Jessica S. W. Borgers
Maartje W. Rohaan
Kristen N. Balogh
Asaf Poran
Michael Rooney
Jesse Z. Dong
John R. Srouji
Vikram R. Juneja
Christina M. Arieta
Cynthia M. Nijenhuis
Bastiaan Nuijen
Mark DeMario
Kelledy Manson
Ton N. M. Schumacher
Richard B. Gaynor
John B. Haanen
Joost H. van den Berg
Marit M. van Buuren