Beclin1‑armed oncolytic Vaccinia virus enhances the therapeutic efficacy of R‑CHOP against lymphoma in vitro and in vivo

Xie,Shufang; Fan,Weimin; Yang,Chen; Lei,Wen; Pan,Hongying; Tong,Xiangmin; Wu,Yi; Wang,Shibing

doi:10.3892/or.2021.7942

Beclin1‑armed oncolytic Vaccinia virus enhances the therapeutic efficacy of R‑CHOP against lymphoma in vitro and in vivo

Authors:
- Shufang Xie
- Weimin Fan
- Chen Yang
- Wen Lei
- Hongying Pan
- Xiangmin Tong
- Yi Wu
- Shibing Wang
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Affiliations: The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310000, P.R. China, Molecular Diagnosis Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P.R. China, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Hematology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
Published online on: January 19, 2021 https://doi.org/10.3892/or.2021.7942
Pages: 987-996
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑Hodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of patients with DLBCL are successfully cured via first‑line Rituximab, Cyclophosphamide, Epirubicin, Vindesine, Prednisolone (R‑CHOP) treatment. However, 30‑40% of patients with DLBCL ultimately suffer from treatment‑refractory or relapsed disease. These patients often suffer from high mortality rates owing to a lack of suitable therapeutic options, and all patients are at a high risk of serious treatment‑associated dose‑dependent toxicity. As such, it is essential to develop novel treatments for NHL that are less toxic and more efficacious. Oncolytic Vaccinia virus (OVV) has shown promise as a means of treating numerous types of cancer. Gene therapy strategies further enhance OVV‑based therapy by improving tumor cell recognition and immune evasion. Beclin1 is an autophagy‑associated gene that, when upregulated, induces excess autophagy and cell death. The present study aimed to develop an OVV‑Beclin1 therapy capable of inducing autophagic tumor cell death. OVV‑Beclin1 was able to efficiently kill NHL cells and to increase the sensitivity of these cells to R‑CHOP, thereby decreasing the dose‑dependent toxic side effects associated with this chemotherapeutic regimen. The combination of OVV‑Beclin1 and R‑CHOP also significantly improved tumor growth inhibition and survival in a BALB/c murine model system owing to the synergistic induction of autophagic cell death. Together, these findings suggest that OVV‑Beclin1 infection can induce significant autophagic cell death in NHL, highlighting this as a novel means of inducing tumor cell death via a mechanism that is distinct from apoptosis and necrosis.

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