Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors

Sep 21, 2026

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Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs) that detect tumor-associated antigens (TAAs), with strong evidence in hematological cancers. However, solid tumors pose obstacles such as immune-suppressing microenvironments and inadequate infiltration.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

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1. Introduction

2. Therapeutic Potential of CAR-T Cells in Solid Tumors

2.1. Current Status of CAR-T Cell Therapy

Review Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors Ruxandra Ilinca Stilpeanu 1, Bianca Stefania Secara 1, Mircea Cretu-Stancu 2,* and Octavian Bucur 1,2,3, * Citation: Stilpeanu, R.I.; Secara, B.S.; Cretu-Stancu, M.; Bucur, O. Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors. Int. J. Mol. Sci. 2024, 25, 11127 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252011127 Academic Editor: Richard H. W. Funk Received: 18 August 2024 Revised: 25 September 2024 Accepted: 30 September 2024 Published: 16 October 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; [bianca.secara@stud.umfcd.ro](bianca.secara@stud.umfcd.ro) (B.S.S.) 2 Genomics Research and Development Institute, 020021 Bucharest, Romania 3 Viron Molecular Medicine Institute, Boston, MA 02108, USA * [Correspondence: mircea.cta@gmail.com](Correspondence: mircea.cta@gmail.com) (M.C.-S.); octavian.bucur@gmail.com or [octavian.bucur@genomica.gov.ro](octavian.bucur@genomica.gov.ro) (O.B.) Abstract: Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs) . Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish the groundwork for their applications on a wide range of requirements. However, the application of CAR-T cell technology for solid tumors has several challenges, such as the existence of an immune-suppressing tumor microenvironment and/or inadequate tumor infiltration. Consequently, combining therapies such as CAR-T cell technology with other approaches has been proposed. The effectiveness of combining CAR-T cell with oncolytic virus therapy, with either genetically altered or naturally occurring viruses, to target tumor cells is currently under investigation, with several clinical trials being conducted. This narrative review summarizes the current advancements, opportunities, benefits, and limitations in using each therapy alone and their combination. The use of oncolytic viruses offers an opportunity to address the existing challenges of CAR-T cell therapy, which appear in the process of trying to overcome solid tumors, through the combination of their strengths. Additionally, utilizing oncolytic viruses allows researchers to modify the virus, thus enabling the targeted delivery of specific therapeutic agents within the tumor environment. This, in turn, can potentially enhance the cytotoxic effect and therapeutic potential of CAR-T cell technology on solid malignancies, with impactful results in the clinical setting. Keywords: oncolytic virus; chimeric antigen receptor T cell; CAR T cell; genetically engineered T cell; immunotherapy 1. Introduction The rising incidence and mortality rates observed annually [1] remain firm arguments for the ongoing prevalence of cancer. The emergence of targeted therapies in cancer molecular medicine and immuno-oncology in recent years has revolutionized the field of cancer treatment [2] . The use of anti-tumor immunotherapy has marked a significant breakthrough in the process of treating cancer by modifying the immune syste

FAQs

What challenges limit CAR-T cell therapy in solid tumors?

Solid tumors often create an immune-suppressing tumor microenvironment and can hinder adequate tumor infiltration, reducing CAR-T effectiveness.

How can oncolytic viruses improve CAR-T outcomes when combined?

Combining oncolytic viruses with CAR-T can increase tumor cell permeability for T cells and reduce immune system interference, potentially improving CAR-T activity against solid tumors.

Why are oncolytic viruses considered promising in this therapeutic context?

Oncolytic viruses selectively replicate in cancer cells, helping destroy them while sparing normal tissues, and they may be engineered for targeted delivery within the tumor environment.

Sep 21, 2026

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