Abstract 6797: Oncolytic virotherapy with non-human viruses to improve anti-myeloma effect
Authors: Marchica Valentina , Vescovini Rosanna , Franceschi Valentina , Storti Paola , Iannozzi Nicolas Thomas , Raimondi Vincenzo , Longu Oxana , Garcia Jessica Burroughs , Toscani Denise , Palma Anna Benedetta Dalla , Donofrio Gaetano , Giuliani Nicola 
Published: April 2023

Abstract
Multiple myeloma (MM) is an incurable hematological malignancy characterized by remission and relapse with drugs resistance. Therefore, new therapeutic approaches are needed. Oncolytic viruses (OVs) represent a new strategy to augment the spectrum of cancer therapeutics. Several studies reported that, in MM, the OVs act through tumor-specific oncolysis and generation of an antitumor immune response. The main viruses that have been tested for MM setting are human viruses, this approach is highly restricted by pre-existing anti-virus humoral immunity that neutralize the anti-tumor effect of OVs. Recently, our group have demonstrated for the first time the role of a bovine virus, non-pathogen for the human, Bovine Viral Diarrhea Virus (BVDV) in direct MM cell killing suggesting its possible use as alternative strategy in MM oncolytic virotherapy. The aim of this study was to increase the bovine oncolytic viruses’s spectrum for anti-MM treatment investigating the role of another bovine virus, Bovine Herpes Virus type 1 (BoHV-1), in the direct effect on MM cells. Firstly, after virus preparation, we treated human MM cell lines (HMCLs) for 24, 48 and 72 hours with BoHV-1 at 1 and 2 multiplicity of infection (MOI). We showed a significant increase of cell mortality, checked by flow cytometry analysis, already after 48 hours of infection in JJN3 (BoHV-1 1 MOI vs untreated p&lt; 0.001; BoHV-1 2 MOI vs untreated p&lt; 0.001) and in MM1.S (BoHV-1 1 MOI vs untreated p= 0.025; BoHV-1 2 MOI vs untreated p= 0.002). Interestingly, the cytotoxic effect of BoHV-1 treatment in HMCLs was associated by a significant increased expression of apoptotic markers as Apo2.7, evaluated by flow cytometry (JJN3 at 48 hours: BoHV-1 1 MOI vs untreated p= 0.007; BoHV-1 2 MOI vs untreated p= 0.001. MM1.S at 48 hours: BoHV-1 1 MOI vs untreated p&lt; 0.001; BoHV-1 2 MOI vs untreated p&lt; 0.001). Subsequently, we infected bone marrow mononuclear cells (BMMNCs) obtained from MM patients with BohV-1 for 48 and 72 hours. Already after 48 hours of infection, we found that MM cells had significantly increased cell mortality in BoHV-1-treated BMMNCs compared with untreated conditions. Overall, our data indicate that BoHV-1, as BVDV, was able to exert a direct anti-tumor effect on both HMCLs and primary cells from MM patients. In addition, data from ongoing studies will characterize the role of immune microenvironment in bovine oncolytic virotherapy. Focusing on monocytes, NK cells and CD8+ T cells we will explore a possible bovine virus-induced immune response to enhance anti-MM virotherapy. This study will highlight the possible use of non-human OVs as new anti-MM strategy.
Citation Format: Valentina Marchica, Rosanna Vescovini, Valentina Franceschi, Paola Storti, Nicolas Thomas Iannozzi, Vincenzo Raimondi, Oxana Longu, Jessica Burroughs Garcia, Denise Toscani, Anna Benedetta Dalla Palma, Gaetano Donofrio, Nicola Giuliani. Oncolytic virotherapy with non-human viruses to improve anti-myeloma effect. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6797.