# Mengovirus Replicon for Enhanced Oncolytic Virotherapy

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $363,713

## Abstract

ABSTRACT
The potential of oncolytic virotherapy as a cancer treatment has been clearly demonstrated in clinical trials,
however the overall efficacies of currently available oncolytic viruses is modest. It has become clear that a
balance between the oncolytic phase and immune phase of this treatment modality needs to be reached in
order to maximize the potential of cure. Mengovirus, a picornaviral pathogen, represents an improved class of
oncolytic viruses because of its ability to undergo preclinical evaluation in immunocompetent animals including
mice and primates. Mengovirus can cause encephalitis and myocarditis, however, we enhanced its safety by
truncating the polycytidine tract (a pathogenic determinant) and by incorporating neuron and cardiac specific
microRNAs into the viral genome. Treatment with this dual-detargeted virus, vMC24-NC, results in complete
regression of syngeneic mouse multiple myeloma plasmacytomas. However, metastatic recurrence was
observed in 50% of the treated mice indicating a need for improving the immune phase of this virotherapy.
The goal of this proposal is to develop a Mengovirus therapy expressing immunostimulatory proteins in order
to boost the immune phase during the oncolytic phase. Incorporation of foreign genes into picornaviral
genomes is inhibited by their limited insertion capacity. Therefore we developed a Mengovirus-based replicon
where the genes encoding the capsid proteins were replaced with a secreted luciferase gene. This replicon
results in foreign gene expression, genome replication, and encapsidation with short-term spread when co-
administered with vMC24-NC. We hypothesize that we can improve the overall spread of the replicon construct
by creating a co-dependence system with an additional helper replicon encoding the capsid proteins and/or
optimizing the treatment protocol based on dose, ratio, and sequence of replicon and helper/virus
administration. These studies will produce for the first time a single-shot system where a potent and safe
oncolytic picornavirus can be armed with immunostimulatory proteins and tested in immunocompetent animals
resulting in a superior oncolytic virotherapy. With this in mind, we propose the following specific aims:
Aim 1. Compare the efficiency of spread and genetic stability of our capsid-substituted (vector) replicons in
cells coinfected with a) replication-competent vMC24-NC or b) capsid-encoding vMC24-NC derived (helper)
replicons that are co-dependent with the vector replicon for nonstructural protein functions.
Aim 2. Determine how the efficiency of intratumoral vector genome expression and spread is impacted by (i)
relative dose of vector and helper (ii) temporal sequencing of vector and helper.
Aim 3. Evaluate the therapeutic efficacy of combination therapies using immunostimulatory Mengovirus
replicons with vMC24-NC or helper replicons.

## Key facts

- **NIH application ID:** 10004586
- **Project number:** 5R01CA207386-05
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Autumn Schulze
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,713
- **Award type:** 5
- **Project period:** 2016-09-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004586

## Citation

> US National Institutes of Health, RePORTER application 10004586, Mengovirus Replicon for Enhanced Oncolytic Virotherapy (5R01CA207386-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004586. Licensed CC0.

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