[Development of CAR-T Cells Effective against Solid Tumors]

Traditionally, the 3 major standard treatments for cancers-surgery, chemotherapy, and radiation therapy-have been applied and have saved many lives. However, malignancies have been the leading cause of death in Japan for more than 40 years since 1981, and the trend is still accelerating. According to the statistics report from the Ministry of Health, Labour and Welfare, cancers accounted for 26.5% of all deaths in 2021, which means that about 1 in 3.5 of all deaths in Japan was due to cancers. Additionally, medical expenditure spent on the diagnosis and treatments for cancer patients have significantly increased, contributing to the pressure on the Japanese economy. Therefore, there is a demand to develop the novel technologies concerning diagnostic methods, effective treatment, and recurrence prevention of cancers. Chimeric antigen receptor(CAR)-T cell therapy has attracted much attention as the next generation of cancer immunotherapy following immune checkpoint blockade therapy, which was the subject of the 2018 Nobel Prize in Physiology or Medicine. CAR-T cell therapy was first approved in the United States in 2017, followed by the EU in 2018 and Japan in March 2019, after having demonstrated significant therapeutic efficacies against B-cell malignancies in clinical trials. However, current CAR-T cell therapies are not yet complete, and there still remain challenges to be overcome. In particular, it is one of the most important issues that current CAR-T cell therapies do not work effectively against solid cancers, which make up the majority of malignant tumors. This review provides an overview of the development toward establishing the next generation CAR-T cell therapy with therapeutic potential against solid cancers.