[Cancer Immunotherapy Using Gene Modification Technology]

Recently, accumulating discoveries in the field of immunology have been applied in clinical settings along with rapid progression of basic and pre-clinical research. Especially, advancement of gene modification technologies has contributed to unlock a way to novel cancer immunotherapy. One representative is chimeric antigen receptor-expressing T(CAR-T)cell therapy which was approved by FDA in August, 2017 as first gene-modified cell therapy. However, such technologies are still work-in-progress and there are many obstacles to be overcome for their full development. So called 4th generation CAR-T cells, in which CAR-T cells are engineered to secrete some kinds of cytokine and/or chemokine, have revealed their prominent potential to eradicate established solid tumors, which are usually resistant to conventional CAR-T cells. Another example of gene-modified cells for cancer immunotherapy is T cell receptor(TCR)-T cells, which are T cells engineered to express tumor antigen-specific TCR. Targeting neoantigens, mutated proteins to be expressed only in cancer cells and scarcely in normal ones, is attracting attempt for TCR-T cell approach. In addition, due to unique immunological functions, other lymphocyte subsets such as natural killer(NK)cells, invariant natural killer T(iNKT)cells, and gd-type T cells gain attention as effector cells to be gene-modified. Furthermore, off-the-shelf cell therapy, in which patients receive cell products made from allogeneic non-self immune cells, is nowunder development. It should be noted that development of "personalized" medicine, which aims to customize drugs to be suitable for each patient and different types of tumor, and "universal" technologies, which are crucial to generate uniform quality of cell products and to decrease manufacturing time and cost, are highly important for further advance of cancer immunotherapy.