June 27, 2022

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T cells expressing MDA-7/IL-24 can broadly recognize and kill cancer

Cancer Res: T cells expressing MDA-7/IL-24 can broadly recognize and kill cancer


T cells expressing MDA-7/IL-24 can broadly recognize and kill cancer.  In previous studies, scientists have discovered that a protein called IL-24 attacks various cancers in many different ways.

In a new study, through T cell engineering, researchers from Virginia Commonwealth University found that using T cells to deliver the gene encoding IL-24 (called MDA-7) to solid tumors can prevent a variety of cancers The tumor grows and inhibits the spread of cancer to other tissues.

The relevant research results were published in Cancer Research in May 2021, with the title of the paper “Engineering T Cells to Express Tumoricidal MDA-7/IL24 Enhances Cancer Immunotherapy”.

 

T cells expressing MDA-7/IL-24 can broadly recognize and kill cancer. 

 


These authors say that their research work has expanded the scope of immunotherapy, and their methods are not very dependent on specific targets expressed by cancer cells. After all, this is not the first time T cells have been designed for cancer immunotherapy.

Chimeric antigen receptor (CAR) T cell (CAR-T) therapy approved by the US Food and Drug Administration (FDA) to destroy cancer cells expressing specific surface molecules has been shown to treat advanced cancers in the blood and lymphatic system A huge success.

However, CAR-T cells have made limited progress in the treatment of solid tumors such as prostate cancer or melanoma, because the cells that make up these tumors are not exactly the same, which hinders the recognition and attack of engineered T cells on tumor cells.


These authors armed T cells with MDA-7/IL-24 to target cancer more broadly. They genetically modified T cells to express MDA-7/IL-24, allowing these T cells to kill cancer cells, regardless of whether the latter express the target molecule. This will help prevent cancer cells from evading immune attacks.


At the subcellular level, MDA-7/IL-24 binds to receptors on the cell surface and instructs them to make and release more MDA-7/IL-24 protein. If the cell is normal, the protein is only secreted and no damage will occur. But if the cell is a cancer cell, MDA-7/IL-24 can cause oxidative stress damage and eventually cell death, which not only occurs in the primary tumor, but also occurs in distant metastases—90 The cause of death in% of patients.

As a result of this process, the immune system produces memory T cells that can theoretically kill the tumor when it recurs. At the entire tumor level, IL-24 also prevents the formation of blood vessels, causing the tumor to lose the nutrients needed to maintain its uncontrolled growth. In mice with prostate cancer, melanoma, or other metastatic cancers, T cells that express MDA-7/IL-24 (ie, MDA-7/IL-24 T cells) slow down more than unmodified T cells Or stop cancer from progressing.

 

T cells expressing MDA-7/IL-24 can broadly recognize and kill cancer. 


Control mice (upper left) with prostate cancer showed large areas of metastatic lesions (blue) in the lungs. When a portion of the mice were treated with unmodified T cells (upper right), their secondary tumors were smaller than those in untreated mice. When another group of mice received genetically modified T cells expressing MDA-7/IL-24 (lower side), the metastatic lesions shrank more, and in some cases even shrank to none. The picture is from Cancer Research, 2021, doi:10.1158/0008-5472.CAN-20-2604.

These authors also found that arming T cells with MDA-7/IL-24 enables them to survive better and proliferate in the tumor microenvironment. The tumor microenvironment is usually very detrimental to immune cells. They found that MDA-7/IL-24 can help T cells proliferate and exceed the number of cancer cells.

Clinically, this method will involve extracting the patient’s own T cells from tumor samples, genetically modifying them to express MDA-7/IL-24, and culturing them in the laboratory to produce millions of cells. Finally, they are transplanted back into the patient. Under the manufacturing standards authorized by the US Federal Government, this method is generally safe and minimally invasive. CAR-T cells may also express MDA-7/IL-24 after genetic modification.

For best results, MDA-7/IL-24 T cells may be used with other therapies. Although bringing this technology from the laboratory to the bedside is no easy task, these authors are optimistic that most of the basic work has been laid.

Clinical trials using different methods to deliver IL-24 for the treatment of several cancers are already underway. A phase 1 clinical trial that uses adenovirus to deliver MDA-7/IL24 to tumors has shown that it has approximately 44% efficacy against various forms of cancer and is generally non-toxic.

These authors have recently jointly received funding from the National Cancer Institute to optimize their technology for the treatment of solid tumors and cancer metastasis, in anticipation of future human clinical trials.

 

(source:internet, reference only)


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