[HTML][HTML] Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity
SR Walsh, D Bastin, L Chen, A Nguyen… - The Journal of …, 2019 - Am Soc Clin Investig
SR Walsh, D Bastin, L Chen, A Nguyen, CJ Storbeck, C Lefebvre, D Stojdl, JL Bramson…
The Journal of Clinical Investigation, 2019•Am Soc Clin InvestigDespite its success in treating melanoma and hematological malignancies, adoptive cell
therapy (ACT) has had only limited effects in solid tumors. This is due in part to a lack of
specific antigen targets, poor trafficking and infiltration, and immunosuppression in the tumor
microenvironment. In this study, we combined ACT with oncolytic virus vaccines (OVVs) to
drive expansion and tumor infiltration of transferred antigen-specific T cells and
demonstrated that the combination is highly potent for the eradication of established solid …
therapy (ACT) has had only limited effects in solid tumors. This is due in part to a lack of
specific antigen targets, poor trafficking and infiltration, and immunosuppression in the tumor
microenvironment. In this study, we combined ACT with oncolytic virus vaccines (OVVs) to
drive expansion and tumor infiltration of transferred antigen-specific T cells and
demonstrated that the combination is highly potent for the eradication of established solid …
Despite its success in treating melanoma and hematological malignancies, adoptive cell therapy (ACT) has had only limited effects in solid tumors. This is due in part to a lack of specific antigen targets, poor trafficking and infiltration, and immunosuppression in the tumor microenvironment. In this study, we combined ACT with oncolytic virus vaccines (OVVs) to drive expansion and tumor infiltration of transferred antigen-specific T cells and demonstrated that the combination is highly potent for the eradication of established solid tumors. Consistent with other successful immunotherapies, this approach elicited severe autoimmune consequences when the antigen targeted was a self-protein. However, modulation of IFN-α/-β signaling, either by functional blockade or rational selection of an OVV backbone, ameliorated autoimmune side effects without compromising antitumor efficacy. Our study uncovers a pathogenic role for IFN-α/-β in facilitating autoimmune toxicity during cancer immunotherapy and presents a safe and powerful combinatorial regimen with immediate translational applications.
The Journal of Clinical Investigation