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One Plus One Is Greater Than Two—Oncolytic Virus and CAR-T Cells Combined to Fight Tumor

Author: Candy Swift
by Candy Swift
Posted: Oct 30, 2020
oncolytic virus

Recently, in a new research, scientists at the City of Hope National Medical Center in the United States combined two immunotherapies, oncolytic virus and chimeric antigen receptor (CAR) T cell therapy, to overcome the impact of the tumor micro-environment, which have successfully targeted and eradicated solid tumors that were difficult to treat with CAR-T therapy alone.

The study was published on September 2, 2020 in Science Translational Medicine, entitled Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. So what exactly this combination therapy is? Will it be a powerful weapon to fight against the tumor? This article will explain more about these two therapies and the latest research of their combination.

  • What is the oncolytic virus?

Oncolytic virus is a kind of tumor-killing virus with replication ability. It can selectively infect tumor cells, then replicate in the cells and finally lyse them. What’s more, it can stimulate the body to produce a specific anti-tumor immune response.

Oncolytic viruses can selectively replicate in tumor cells, enhance the immunogenicity of the tumor microenvironment, and trigger a broad tumor immune response. It also has a multi-channel killing mechanism, and can act on multiple links of tumor immunity, which, with broad-spectrum anti-tumor properties, is effective against recurring and metastatic tumors. In addition, oncolytic viruses are usually safe with few side effects, thus oncolytic virotherapy for combination therapy has been widely studied.

"Since the German scientist Jean Rommelaere first referred to oncolytic virus therapy as tumor immunotherapy in 2011, oncolytic virus has now been accepted by the public as an important branch of tumor immunotherapy." introduced by a scientist at Creative Biolabs, an oncolytic virus related services and products provider in the US.

  • What is CAR-T cell?

CAR is an artificially constructed chimeric receptor that can specifically recognize and bind tumor-associated antigens. CAR-T cells are formed by the fusion of antibody single-chain variable regions that can recognize tumor antigens and T cell signaling molecules.

CAR-T cells not only perform the characteristic of specifically binding tumor antigens, but also have the activity of targeting tumor cells. Today, CAR technology has experienced three generations of development. Compared with the first-generation, the second and third-generation CAR technology can significantly prolong the survival time of CAR-T cells in the body, and increase the cytotoxic activity, proliferation ability, and cytokine release, thereby exerting a sustained anti-tumor effect in vivo.

  • Research results and future development of the novel combination therapy

In the study, scientists from the City of Hope genetically engineered the oncolytic virus to allow the oncolytic virus to enter tumor cells and make the cancer cells express CD19 protein on the cell surface. Scientists then use CAR T cells targeting CD19 to identify and attack these solid tumors.

The researchers first created an oncolytic virus (OV19t), which can enter tumor cells and produce truncated CD19 (CD19t). They successfully did this in triple-negative breast cancer cell lines, pancreatic cancer, prostate cancer, ovarian cancer, head and neck cancer, and brain tumor cells. Then the CD19-targeted CAR T cells were combined with OV19t and treated the tumor cells in mice.

CD19-targeted CAR T cell therapy has been approved by the US Food and Drug Administration and can be used to treat certain types of blood cancers, such as B-cell lymphoma and acute lymphoblastic leukemia. This new study may expand the use of these cells in the treatment of patients with solid tumors.

The research also proved that mice that had been treated with a combination of oncolytic virus and CAR T cells showed long-term anti-tumor immune protection. Researchers are currently designing a clinical trial to test this combination therapy in patients. The trial will first test the safety of OV19t in patients with solid tumors. If it can be proved to be safe and effective, then oncolytic virus and CAR T cell therapy can be tested in turn. The trial is expected to start in 2022.

About the Author

Candy Swift: Focus on the cutting edge biological information around the world.

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Author: Candy Swift
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Candy Swift

Member since: Nov 06, 2019
Published articles: 187

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