Recent experiments exploring the use of patients’ own genetically reprogrammed immune cells toward the treatment of chronic diseases such as HIV and cancer have had encouraging and sometimes high-profile results. Yet, these studies have only been conducted in a limited number of individuals, and outcomes have been inconsistent, ranging from complete remission to complete inefficacy.
Now, two teams of researchers have demonstrated a method of using patients’ cells to create long-lived immune cells that target specific HIV and cancer antigens, and appear to resist degradation over time. Their work was published today in two separate papers in Cell Stem Cell.
“Our method has realized the functional rejuvenation and unlimited production of mature cytotoxic T cells with desired antigen-specificity for the first time in vitro,” says Shin Kaneko a stem cell biologist at Kyoto University in Japan and a co-author of the HIV-related study.
Difficulties in previous attempts to extract and reengineer T cells from patients are thought to be due in part to a phenomenon known as ‘cellular senescence’, a type of aging process. Naïve, quiescent T cells can survive for decades in the body. But active T cells, particularly those expanded outside the body in the laboratory, can gradually lose the ability to proliferate and be effective. This can lead to insufficient numbers of active immune cells to combat disease.
“Replicative senescence is likely to be a major issue for adoptive cell therapy,” says Carl June, an immunologist at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. “[These papers] address this issue and are exciting demonstrations of the progress in cell and developmental biology.”