Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

Oncoimmunology
Jun RenHerbert Kim Lyerly

Abstract

Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods: We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results: Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repe...Continue Reading

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Citations

Dec 30, 2017·Human Gene Therapy·Ding WeiHuijie Bian
Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
Apr 5, 2020·Journal of Hematology & Oncology·Chongxian PanLei Zheng
Dec 5, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Guoliang QiaoHerbert Kim Lyerly
Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
Feb 14, 2018·Cancer Immunology Research·Colleen S CurranElad Sharon
Dec 6, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guoliang QiaoHerbert Kim Lyerly
Jun 15, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ni JiangH Kim Lyerly

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Methods Mentioned

BETA
flow cytometry
electrophoresis
PCR

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