Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin beta1 Blocking Antibody OS2966.

Title

Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin beta1 Blocking Antibody OS2966.

Creator

Lee Tae Jin; Nair Mitra; Banasavadi-Siddegowda Yeshavanth Kumar; Liu Joseph; Nallanagulagari Tejaswini; Jaime-Ramirez Alena Cristina; Guo Jeffrey Yunhua; Quadri Haroon; Zhang Jianying; Bockhorst Kurt H; Aghi Manish K; Carbonell W Shawn; Kaur Balveen; Yoo Ji Young

Publisher

Molecular cancer therapeutics

Date

2019
2019-03

Description

Integrin beta1 receptor, expressed on the surface of tumor cells and macrophages in the tumor microenvironment (TME), has been implicated in both tumor progression as well as resistance to multiple modalities of therapy. OS2966 is the first clinical-ready humanized monoclonal antibody to block integrin beta1 and was recently orphan designated by FDA Office of Orphan Products Development (OOPD). Here, we tested therapeutic potential of OS2966-mediated integrin beta1 blockade to enhance the efficacy of oncolytic herpes simplex virus-1 (oHSV) through evaluation of virus replication, tumor cell killing efficiency, effect on the antiviral signaling pathway, co-culture assays of oHSV-infected cells with macrophages, and in vivo bioluminescence imaging on mammary fat pad triple negative breast cancer xenograft and subcutaneous and intracranial glioma xenografts. OS2966 treatment decreased interferon signaling and pro-inflammatory cytokine induction in oHSV-treated tumor cells and inhibited migration of macrophages, resulting in enhanced oHSV replication and cytotoxicity. OS2966 treatment also significantly enhanced oHSV replication and oHSV-mediated anti-tumor efficacy in orthotopic xenograft models including triple negative breast cancer and glioblastoma. The results demonstrated the synergistic potential of the combinatory treatment approach with OS2966 to improve anti-tumor efficacy of conventional oHSV therapy.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Citation

Lee Tae Jin; Nair Mitra; Banasavadi-Siddegowda Yeshavanth Kumar; Liu Joseph; Nallanagulagari Tejaswini; Jaime-Ramirez Alena Cristina; Guo Jeffrey Yunhua; Quadri Haroon; Zhang Jianying; Bockhorst Kurt H; Aghi Manish K; Carbonell W Shawn; Kaur Balveen; Yoo Ji Young, “Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin beta1 Blocking Antibody OS2966.,” NEOMED Bibliography Database, accessed April 18, 2021, https://neomed.omeka.net/items/show/6306.

Social Bookmarking