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Armed Oncolytic Myxoma Viruses to Eliminate Acute Myeloid Leukemia and Multiple Myeloma Cells

Description

Novel biological strategies for cancer therapy have recently been able to generate antitumor effects in the clinic. Of these new advancements, oncolytic virotherapy seems to be a promising strategy through a dual mechanism of oncolysis and immunogenicity of the host

Novel biological strategies for cancer therapy have recently been able to generate antitumor effects in the clinic. Of these new advancements, oncolytic virotherapy seems to be a promising strategy through a dual mechanism of oncolysis and immunogenicity of the host to the target cells. Myxoma virus (MYXV) is an oncolytic poxvirus that has a natural tropism for European rabbits, being nonpathogenic in humans and all other known vertebrates. MYXV is able to infect cancer cells which, due to mutations, have defects in many signaling pathways, notably pathways involved in antiviral responses. While MYXV alone elicits lysis of cancer cells, recombinant techniques allow for the implementation of transgenes, which have the potential of ‘arming’ the virus to enhance its potential as an oncolytic virus. The implementation of certain transgenes allow for the promotion of robust anti-tumor immune responses. To investigate the potential of immune-inducing transgenes in MYXV, in vitro experiments were performed with several armed recombinant MYXVs as well as unarmed wild-type and rabbit-attenuated MYXV. As recent studies have shown the ability of MYXV to uniquely target malignant human hematopoietic stem cells, the potential of oncolytic MYXV armed with immune-inducing transgenes was investigated through in vitro killing analysis using human acute myeloid leukemia (AML) and multiple myeloma (MM) cell lines. Furthermore, in vitro experiments were also performed using primary bone marrow (BM) cells obtained from human patients diagnosed with MM. In this study, armed MYXV-infected human AML and MM cells resulted in increased cell death relative to unarmed MYXV-infected cells, suggesting enhanced killing via induced mechanisms of cell death from the immune-inducing transgenes. Furthermore, increased killing of primary BM cells with multiple myeloma was seen in armed MYXV-infected primary cells relative to unarmed MYXV-infected primary cells.

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Date Created
2019-05

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Evaluation of Plant-based Viral Vectors for West Nile Virus Antibody Expression Levels

Description

Plant viral vectors have previously been used to produce high expression levels of antibodies and other proteins of interest. By utilizing a transformed Agrobacterium with the vector containing the protein of interest for infiltration, viral vectors can easily reach the

Plant viral vectors have previously been used to produce high expression levels of antibodies and other proteins of interest. By utilizing a transformed Agrobacterium with the vector containing the protein of interest for infiltration, viral vectors can easily reach the plant cells making it an effective form of transient protein expression. For this project two different plant viral vectors were compared; the geminiviral vector derived from Bean yellow dwarf virus (BeYDV) and the MagnICON vector system derived from Tobacco Mosaic Virus(TMV) and Potato Virus X(PVX). E16, an antibody against West Nile virus, has previously been expressed using both systems but expression levels between the systems were not directly compared. Agrobacterium tumefaciens EHA105 cells were transformed with both systems and expression levels of E16 were quantified using ELISAs. Results showed very low expression levels of E16 using the geminiviral vector indicating a need for further investigation into the clone used as previous studies reported much higher expression levels with the system.

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Date Created
2020-05