@article{1b2ed672a28647b8988559cfd03e79b5,
title = "A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity",
abstract = "Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.",
author = "Kim, {Miriam Y.} and Reyka Jayasinghe and Devenport, {Jessica M.} and Ritchey, {Julie K.} and Rettig, {Michael P.} and Julie O{\textquoteright}Neal and Staser, {Karl W.} and Kennerly, {Krista M.} and Carter, {Alun J.} and Feng Gao and Lee, {Byung Ha} and Cooper, {Matthew L.} and DiPersio, {John F.}",
note = "Funding Information: The authors thank Julia Hollaway, Susan Gladney, Emily Street, Nicholas Wallace, and Kevin Kowal for assistance with animal care and experimental procedures and Sara Ferrando-Martinez and Alexandra Wolfarth for their critical review of the manuscript. We also thank the Siteman Flow Cytometry Core and the McDonnell Genome Institute at Washington University for providing technical assistance and equipment, and the Division of Comparative Medicine at Washington University for their excellent animal care. M.Y.K. was supported by an Alex{\textquoteright}s Lemonade Stand Foundation/Northwestern Mutual Young Investigator Award, a Washington University SPORE in Leukemia Developmental Research Award, and a Dean{\textquoteright}s Scholars Award from the Washington University Division of Physician-Scientists, which is funded by a Burroughs Wellcome Fund Physician-Scientist Institutional Award. M.P.R. was supported by an NCI Research Specialist Award (R50 CA211466). J.O. was supported by the International Myeloma Society and Paula and Roger Riney Foundation Translational Research Grant. J.F.D. was supported by an NCI Outstanding Investigator Award (R35 CA210084), an NIH P50 CA171963, and a Children{\textquoteright}s Discovery Institute Award. Funding Information: The authors thank Julia Hollaway, Susan Gladney, Emily Street, Nicholas Wallace, and Kevin Kowal for assistance with animal care and experimental procedures and Sara Ferrando-Martinez and Alexandra Wolfarth for their critical review of the manuscript. We also thank the Siteman Flow Cytometry Core and the McDonnell Genome Institute at Washington University for providing technical assistance and equipment, and the Division of Comparative Medicine at Washington University for their excellent animal care. M.Y.K. was supported by an Alex{\textquoteright}s Lemonade Stand Foundation/Northwestern Mutual Young Investigator Award, a Washington University SPORE in Leukemia Developmental Research Award, and a Dean{\textquoteright}s Scholars Award from the Washington University Division of Physician-Scientists, which is funded by a Burroughs Wellcome Fund Physician-Scientist Institutional Award. M.P.R. was supported by an NCI Research Specialist Award (R50 CA211466). J.O. was supported by the International Myeloma Society and Paula and Roger Riney Foundation Translational Research Grant. J.F.D. was supported by an NCI Outstanding Investigator Award (R35 CA210084), an NIH P50 CA171963, and a Children{\textquoteright}s Discovery Institute Award. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30860-0",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}