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.

Published

Journal Article

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 repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions: Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

Full Text

Duke Authors

Cited Authors

  • Ren, J; Gwin, WR; Zhou, X; Wang, X; Huang, H; Jiang, N; Zhou, L; Agarwal, P; Hobeika, A; Crosby, E; Hartman, ZC; Morse, MA; H Eng, K; Lyerly, HK

Published Date

  • January 2017

Published In

Volume / Issue

  • 6 / 4

Start / End Page

  • e1264563 -

PubMed ID

  • 28507788

Pubmed Central ID

  • 28507788

Electronic International Standard Serial Number (EISSN)

  • 2162-402X

International Standard Serial Number (ISSN)

  • 2162-4011

Digital Object Identifier (DOI)

  • 10.1080/2162402X.2016.1264563

Language

  • eng