The human induced pluripotent stem cell (iPSC) research landscape is rapidly evolving. We recently discussed the current trend in stem cell research to streamline the production of induced pluripotent stem cells (iPSC) from peripheral blood mononuclear cells (PBMCs). Recent exciting studies have indicated that harnessing iPSCs self-renewal ability to manufacture cell therapies is now becoming a reality. Just 4 years ago, the pharmaceutical company Takeda and The Center for iPS Cell Research and Application (CiRA) at Kyoto University entered a 10-year joint research collaboration. A few weeks ago, it was announced that Takeda has advanced the first product from its collaboration with CiRA - a highly scalable off-the-shelf CAR-T cell therapy to treat cancer - into pre-clinical development. Here, we briefly discuss the iCART science behind the Takeda study and its potential implications for an “off-the-shelf” CAR-T cell therapy.
iCART and iPSCs
The iCART technology was developed by the Kyoto-based CiRA research center founded in 2010 and led by Prof. Shinya Yamanaka, who went on to win the Nobel Prize for Physiology or Medicine in 2012 for his research that led to the first iPSC created from mature cells. This groundbreaking work demonstrated for the first time that it was possible in vitro to induce a mature, somatic cell to become a stem cell. Providing a ready source of stem cells for use in the development of cell therapy products and ushering in the current era of cell therapy.
The iCART technology extends the original Nobel Prize-winning research and has the potential to usher in its own new wave of cell therapies. The iCART program is a next-generation approach to develop off-the-shelf CAR-T cell therapies. It differs from current methods of allogeneic cell therapy in that instead of relying on cells derived from a donor for each individual treatment, the iCART process creates a clonal master iPSC bank; essentially, creating a much larger pool of cells that can be repeatedly drawn upon to produce on-demand, tailorable immunotherapies for patients.
By drawing on a stable bank of homogenous iPS cells, the iCART technology could potentially lead to a much more scalable process able to deliver larger quantities of homogenous therapeutic cells. The technology also has the potential to dramatically reduce the cost and complexity associated with current CAR-T therapies.
The first therapies resulting from the iCART project are licensed to Takeda under the on-going, collaborative T-CiRA program, and is expected to be one of five CAR-T programs currently in development by Takeda with planned first-in-human studies by 2021.
At the core of the iCART technology is the iPS cell bank. The creation of which involves the collection of cells from healthy donors with homozygous HLA (human leukocyte antigen). This starting donor material (peripheral blood in this case) is then induced in order to create the iPS clonal cell bank. Once established, this cell bank can be drawn upon multiple times, providing source material for the research, development, and manufacture of cell treatments for patients.
Below in figure 1 shows a schematic of the process in which iPSCs can be reprogrammed from PBMCs or T cells isolated from human donor peripheral blood.
Figure1: Overview of iPSC derivation from healthy donor peripheral blood
iPSCs have revolutionized regenerative medicine within such a short span of time. Even though iPSC-based therapeutic approaches are still in their infancy, with some hurdles for effective translation to overcome, it is highly likely that we will see the true potential of iPSCs in the clinical settings within the next year or so.
iPSC-Derived CAR T-Cell Therapy Created by Kyoto University CiRA and Takeda Collaboration Enters Process Development Toward Clinical Testing. Press Release July 2019