Nowadays, cancer has been recognized as the prime enemy of human health. In the thousands of years of cancer-fighting history, human beings have never retreated from fighting with bare hands to evolving into a high-tech war on all fronts. Cell immunotherapies are part of the high-tech weapons to overcome cancer, which have overcome the challenges and made many outstanding research advances.
When it comes to CAR-T therapy, many scientists are familiar with this superstar in the troop of cell therapies. CAR-T technology has shown remarkable efficacy in a variety of blood cancers, such as leukemia, lymphoma, and multiple myeloma. However, the clinical efficacy of CAR-T therapy in solid tumors is not satisfactory.
The reasons for this are mainly due to the difficulties in cell therapy for solid tumors, such as the large heterogeneity of different types of solid tumors, the lack of unique tumor-associated antigens as CAR-T targets, the inability of T cells to effectively home to the tumor site, the lack of CAR-T cell persistence, and the complex microenvironment within the tumor that has a suppressive effect on immunity.
However, these difficulties are being addressed as in a new study, researchers from the Mayo Clinic designed immunotherapy that combines CAR T cell therapy with an oncolytic virus to more effectively target and treat solid tumors. The findings are published on April 13, 2022 in Science Translational Medicine titled Oncolytic virus-mediated expansion of dual-specificity CAR T cells improves efficacy against solid tumors in mice.
This combination therapy involves loading an oncolytic virus into CAR-T cells that have been genetically modified to seek out cancer cell surface antigens. As naturally occurring viruses, oncolytic viruses can infect and kill cancer cells. They either replicate well naturally in cancer cells or can be modified to selectively target cancer cells.
This new study shows that CAR-T cells can help deliver oncolytic viruses into solid tumors. The viruses can then infiltrate the tumor cells, replicate, cause the tumor cells to burst open, and stimulate a powerful immune response.
The investigators also found that this CAR-T and oncolytic virus combination therapy provided an immunological memory phenotype against solid tumors. Loading oncolytic virus onto CAR-T cells activated their resistance against the virus and the tumor, and they gained immunological memory. This allowed for reinforcement at a later time point, which in turn allowed CAR-T cells to reawaken and perform additional tumor killing.
Using mouse models, the team delivered this combination therapy by intravenous injection to treat advanced gliomas, as well as melanomas in the skin. They found that this combination therapy resulted in high cure rates of tumors at multiple sites without causing significant toxic effects. They also found that this combination therapy produced significant protection against tumor recurrence in cured mice.
How research in animal models can be translated into treatments for patients needs to be further studied through clinical trials. As research on various types of cell therapies proceeds, it seems that humans are getting closer to the end of a complete cure for cancer, and that the long history of the battle between humans and cancer will one day come to an end.
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