Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and DualTargeted Coxsackievirus B3 - Abstract & Key Findings

Sep 21, 2026

Uploaded by Patrick

Breast cancer’s immunosuppressive microenvironment limits immunotherapy, while oncolytic viruses face barriers from neutralizing antibodies and rapid immune clearance. This study investigates microRNA-modified coxsackievirus B3 (miR-CVB3) and its use with bioengineered immunostimulatory exosomes to reshape immune signaling. miR-CVB3 reprograms immune-related protein profiles toward a more immunostimulatory phenotype and enhances exosome-mediated activation of immune cells. ExomiR-CVB3 retains antitumor cytotoxicity, shields miR-CVB3 from antibody neutralization, and strengthens immune effects after systemic administration. An engineered variant, ExomiR-CVB3/DoxApt, combines AS1411 aptamer decoration and doxorubicin for improved efficacy. In vitro and in vivo analyses show selective tumor targeting, tumor cell death, and strong immune infiltration while sparing healthy organs, supporting a versatile immunotherapy platform.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

Breast cancer burden and treatment limitations

Rationale for oncolytic viruses

Figure 1 Overview

Immunomodulatory protein changes in infected cells and exosomes

ExomiR-CVB3 structure and marker expression

This article is licensed under CC-BY-NC-ND 4.0 | [www.acsnano.org](www.acsnano.org)
Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and DualTargeted Coxsackievirus B3
Amirhossein Bahreyni, Yasir Mohamud, Sanaz Ashraf Nouhegar, Jingchun Zhang, and Honglin Luo*
Cite This: ACS Nano 2024, 18, 4241−4255

Read Online | | | | | | | --- | --- | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | ABSTRACT: Breast cancer’s immunosuppressive environment hinders effective immunotherapy, but oncolytic viruses hold promise for addressing this challenge by targeting tumor cells and altering the microenvironment. Yet, neutralizing antibodies and immune clearance impede their clinical utility. This study explored microRNA-modified coxsackievirus B3 (miR-CVB3), an innovative oncolytic virus, and its potential in breast cancer treatment. It investigated miR-CVB3’s impact on immune-related proteins and utilized exosomes as both protective shields and delivery carriers. Results demonstrated miR-CVB3’s capacity toreshape immune-related protein profiles toward a more immunostimulatory state and enhance exosome-mediated immune cell activation. Notably, cancer cell-released exosomes encapsulating miR-CVB3 (ExomiR-CVB3) maintained its antitumor cytotoxicity and bolstered its immunostimulatory effects. Moreover, ExomiR-CVB3 shielded miR-CVB3 from neutralizing antibodies and rapid immune clearance when it was systemically administered. Building on these findings, ExomiR-CVB3 was engineered with the AS1411 aptamer and doxorubicin (ExomiR-CVB3/DoxApt), enhancing therapeutic efficacy. This notable approach, combining genomic modification, aptamer surface decoration, and doxorubicin addition, demonstrated safe delivery of CVB3 to cancer cells. Comprehensive in vitro and in vivo analyses revealed selective breast cancer cell targeting, cell death induction, and significant immune cell infiltration within the tumor microenvironment while sparing healthy organs. In summary, this study highlights ExomiR-CVB3/DoxApt as a pioneering breast cancer treatment strategy adaptable for diverse cancer types, offering a potent and versatile approach to reshaping cancer immunotherapy. KEYWORDS: CVB3, breast cancer immunotherapy, exosomes, tumor targeting, oncolytic virus INTRODUCTION Breast cancer stands as the most commonly diagnosed cancer and the second-leading cause of cancer-associated fatalities in women worldwide.1 The available treatment options for breast cancer encompass radiation therapy, surgical procedures, and chemotherapy.2 Despite recent advancements in treatments, the five-year survival rate among patients with breast cancer remains around 25%.3 Current anticancer drugs lack precise discrimination between malignant and normal cells, causing widespread toxicity and adverse effects.4,5 Hence it is imperative to explore effective therapeutic approaches to improve patient outcomes. An oncolytic virus (OV) is a type of virus targeting and replicating within a range of tumor cells while sparing healthy tissues from damage.6 Mechanistically, OVs induce the direct © 2024 The Authors. Published by American Chemical Society lysis of tumor cells while also triggering the release of tumorassociated antigens. Additionally, they facilitate the exposure/ secretion ofpathogen-associated molecular patterns and cellular danger-associated molecular patterns (DAMPs), thereby prompting the initiation of innate and adaptive immune responses that collectively combat and eliminate tumor cells.7 Coxsackievirus B3 (CVB3) is a single-stranded RNA virus Received: September 29, 2023 Revised: December 22, 2023 Accepted: December 27, 2023 Published: January 26, 2024 [https://doi.org/10.1021/acsnano.3c09491](https://doi.org/10.1021/acsnano.3c09491) 4241 ACS Nano 2024, 18, 4241−4255 Article Figure 1. miR-CVB3 infection

FAQs

Why are oncolytic viruses challenging for clinical breast cancer treatment?

Neutralizing antibodies and immune clearance can block oncolytic viruses, limiting their clinical utility. The study addresses these barriers by using exosome-based shielding and delivery.

What is miR-CVB3 and how does it affect the immune environment?

miR-CVB3 is a microRNA-modified coxsackievirus B3 designed for breast cancer treatment. It alters immune-related protein profiles toward a more immunostimulatory state and promotes immune cell activation via exosomes.

How does ExomiR-CVB3 improve antitumor efficacy and immune effects?

Cancer cell-released exosomes encapsulating miR-CVB3 (ExomiR-CVB3) maintain antitumor cytotoxicity and bolster immunostimulatory effects. It also shields miR-CVB3 from neutralizing antibodies and rapid immune clearance after systemic delivery.

What enhancements does ExomiR-CVB3/DoxApt provide over the base approach?

ExomiR-CVB3/DoxApt adds an AS1411 aptamer surface and incorporates doxorubicin to increase therapeutic efficacy. The study reports selective tumor targeting, tumor cell killing, and significant immune infiltration with reduced harm to healthy organs.

Sep 21, 2026

Uploaded by Patrick