Development of immune function-controlling next-generation chimeric antigen receptor T cells, "Prime CAR-T cells," with extremely high therapeutic effects against solid tumors.

A research group led by Professor Koji Tamada, the Department of Immunology, Yamaguchi University Graduate School of Medicine, has been working to develop next-generation chimeric antigen receptor T cell (CAR-T cell) that are given the ability to control immune responses in a body of patients (Proliferation-inducing and migration-enhancing CAR-T cells: Prime CAR-T cells). In the present study, they have developed a new CAR-T cell that has the capacity to simultaneously produce a cytokine called IL-7 and a chemokine called CCL19.
Recently, CAR-T cell therapy has been attracting considerable attention as a breakthrough of cancer immunotherapy because it demonstrates significant effects in several hematological malignancies. However, there remain issues to be overcome such as having a weak efficacy against solid tumors, which account for the majority of cancers.
Prime CAR-T cells demonstrated a remarkable therapeutic effect in mouse solid tumor models for which only a weak effect had been induced by conventional CAR-T cells. The therapeutic effects of the Prime CAR-T cells are achieved by collaboration between the administered CAR-T cells and immune cells of the recipient. They also revealed that administration of the Prime CAR-T cells induced long-term prevention of tumor recurrence.
Conventionally, the function of CAR-T cells had been focused only on the activity to directly kill cancer cells, but the Prime CAR-T cells play a role as a "delivery system" for molecules that regulate immune functions which a recipient inherently possesses. This is a paradigm shift substantively changing the concept of CAR-T cells.
It is anticipated that Prime CAR-T cell technology will immensely expand the application range of CAR-T cell therapy, leading to groundbreaking solid tumor treatments.


This research achievement was published online in Nature Biotechnology (IF = 41.667 (2016)) (DOI: 10.1038/cercor/nbt.4086).