Ke Bai1, Scott M Norberg2, Cem Sievers1, Tanya Meyer3, Jay Friedman1, Christian Hinrichs4, Clint T Allen1. 1. Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. 2. Genitourinary Malignancies Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA. 3. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA. 4. Rutgers Cancer Center, New Brunswick, New Jersey, USA.
Abstract
BACKGROUND: Immune checkpoint blockade can provide clinical benefit for patients with advanced cancer. Here, we report durable disease control over many years following PD-L1 blockade through induction of a viral antigen-specific T cell response in an adult patient with recurrent respiratory papillomatosis. METHODS: Antigen-specific T cell response assays, single cell RNA-sequencing, and RNA-scope was used to study clinical tissues. RESULTS: An HPV6 E2-specific T cell clone restricted to HLA-B*55, present at low frequency in the pre-treatment papilloma, significantly expanded after six doses of PD-L1 blockade and remained present and functional at the site of initial response in the larynx as a tissue resident memory T cell for 4 years. An associated reduction in E2 target gene was observed following treatment. CONCLUSIONS: Although demonstrated in a single exceptional responder, these results highlight that immune checkpoint blockade may induce durable, viral antigen-specific immunity of sufficient magnitude to control disease in patients with nonmalignant disorders.
BACKGROUND: Immune checkpoint blockade can provide clinical benefit for patients with advanced cancer. Here, we report durable disease control over many years following PD-L1 blockade through induction of a viral antigen-specific T cell response in an adult patient with recurrent respiratory papillomatosis. METHODS: Antigen-specific T cell response assays, single cell RNA-sequencing, and RNA-scope was used to study clinical tissues. RESULTS: An HPV6 E2-specific T cell clone restricted to HLA-B*55, present at low frequency in the pre-treatment papilloma, significantly expanded after six doses of PD-L1 blockade and remained present and functional at the site of initial response in the larynx as a tissue resident memory T cell for 4 years. An associated reduction in E2 target gene was observed following treatment. CONCLUSIONS: Although demonstrated in a single exceptional responder, these results highlight that immune checkpoint blockade may induce durable, viral antigen-specific immunity of sufficient magnitude to control disease in patients with nonmalignant disorders.
Authors: Benjamin Y Jin; Tracy E Campbell; Lindsey M Draper; Sanja Stevanović; Bianca Weissbrich; Zhiya Yu; Nicholas P Restifo; Steven A Rosenberg; Cornelia L Trimble; Christian S Hinrichs Journal: JCI Insight Date: 2018-04-19
Authors: Yvette Robbins; Jay Friedman; Paul E Clavijo; Cem Sievers; Ke Bai; Renee N Donahue; Jeffrey Schlom; Andrew Sinkoe; Christian S Hinrichs; Clint Allen; Houssein Abdul Sater; James L Gulley; Scott Norberg Journal: J Immunother Cancer Date: 2021-08 Impact factor: 12.469
Authors: Grace X Y Zheng; Jessica M Terry; Phillip Belgrader; Paul Ryvkin; Zachary W Bent; Ryan Wilson; Solongo B Ziraldo; Tobias D Wheeler; Geoff P McDermott; Junjie Zhu; Mark T Gregory; Joe Shuga; Luz Montesclaros; Jason G Underwood; Donald A Masquelier; Stefanie Y Nishimura; Michael Schnall-Levin; Paul W Wyatt; Christopher M Hindson; Rajiv Bharadwaj; Alexander Wong; Kevin D Ness; Lan W Beppu; H Joachim Deeg; Christopher McFarland; Keith R Loeb; William J Valente; Nolan G Ericson; Emily A Stevens; Jerald P Radich; Tarjei S Mikkelsen; Benjamin J Hindson; Jason H Bielas Journal: Nat Commun Date: 2017-01-16 Impact factor: 14.919
Authors: Jay Friedman; Sreenivasulu Gunti; Maxwell Lee; Ke Bai; Christian Hinrichs; Clint T Allen Journal: BMC Immunol Date: 2022-02-11 Impact factor: 3.615
Authors: Clint T Allen; Sunmin Lee; Scott M Norberg; Damian Kovalovsky; Hong Ye; Paul E Clavijo; Siwen Hu-Lieskovan; Richard Schlegel; Jeffrey Schlom; Julius Strauss; James L Gulley; Jane Trepel; Christian S Hinrichs Journal: J Immunother Cancer Date: 2019-05-03 Impact factor: 13.751