|Health human T cell | NIAID|
Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.
My report this month delves into some pretty complex science, but it is in an area that is integral to stem cell science: our immune systems.
Efforts to fine-tune our immune response can arrive at a therapeutic benefit from many different directions. Two papers this month point to potential therapies from both augmenting and tamping down the immune response. Another paper seeks to produce large armies of immune cells with a very narrow focus, wiping out cancerous blood cells.
Two papers appeared together in the journal Cell Stem Cell, one from a team at the University of California, San Francisco and one from a team at Peking University. They both succeeded in growing functional thymus tissue from embryonic stem cells, something that has evaded past investigators. The tiny thymus gland is necessary to develop fully functional T cells able to recognize foreign invaders, but also able to recognize self and not result in autoimmune disease. These papers point to the possibility of enhancing the immune response in the elderly whose thymus is often worn out, and in cancer patients whose immune cells have been damaged by chemotherapy.
The research also holds out potential for reaching a major long-term goal for stem cell science—producing tissue to repair part of the body and transplanting it without the new cells being recognized as foreign and being destroyed by the immune system. If thymic tissue can be generated from the same stem cells used to create the repair cells, the thymic cells might induce tolerance for the needed repair without immune suppressant drugs.
The lead paper this month appeared in Nature Biotechnology and seeks to scale up a very promising therapy that produced significant clinical results in leukemia patients earlier this year. A team at New York’s Memorial Sloan Kettering Cancer Center and others around the country isolated immune system T cells from patients or donors and genetically modified them so that they would recognize cancerous B cells in the bloodstream. Those cells modified with a technology dubbed CAR, wiped out the cancer and the patients went into remission.
The problem is supply. Many patient’s disease preempts using their own T cells, and often patients can not find a donor that is a close enough immunologic match, and even if they do, donor cells always carry significant risk. The Sloan-Kettering team decided to try to make large quantities of T cells from pluripotent stem cells, the type made by reprogramming adult cells into iPS cells. But they took advantage of one oddity of iPS cells—they seem to retain some memory of the type of cell they were before they were converted. So, the team used mature T cells from healthy donors as the starting point, hoping the resulting iPS cells would more easily mature into T cells. After the stem cells were genetically altered with the CAR technology, they were able to get a 50-fold expansion of the T cells. A strong step toward an off-the-shelf therapy.
We at CIRM are so concerned about the role of immunology in our eventual success that we funded one round of grants all focused on these issues. You can see those awards and read more about them here.
My full report is available online, along with links to my reports from previous months.