While autologous iPSC-based cell therapies are patient-specific, allogeneic iPSC-based cell therapies use donor-derived cells as a starting material. In recent years, a greater number of allogeneic iPSC-derived cell therapies are being studied than autologous therapies. One of the advantages of allogeneic therapy is that a large number of doses can be generated simultaneously from a single batch of iPSCs and banked.
The production process can therefore be “scaled up” and we can achieve economies of scale that reduce the cost of each dose. This method also enables “off-the-shelf” distribution, simplifying logistics and minimizing the time to reach the patient. Reducing the time to patient is most critical for certain acute conditions where the patient requires immediate care.
The major disadvantage of an allogeneic approach is the possibility of immune rejection. Patients have to undergo immunosuppression, which is often associated with an increased risk of infection and cardiovascular defects. One of the strategies is to reduce immune rejection is to set up human leukocyte antigen (HLA)-matched haplobanks, in which donor iPSC lines are manufactured from donors with the most common HLA haplotypes to match a range of patients.
A 100-line HLA-matched bank can usually cover 78% of European-Americans. Yet, it can only cover 52% of Hispanics and <50% of African-Americans, making it difficult for patients from racial and ethnic minority groups to have the treatment. Although HLA matching can minimize the risk of an immune reaction, it can not totally eliminate the need for immunosuppression. Even “immuneprivileged organs”, such as the brain or eye, need short-term immunosuppression for transplantations of HLA-matched cells.
Another way to evade immune rejection in iPSC-derived transplants is using universal, or immunocloaked, cells. Production of these cell lines necessitates multiple rounds of gene editing, in which certain genes are deleted to prevent T-cell invasion, whereas others are left intact or knocked in to prevent NK-cell invasion.
These methods can make it possible to cover the entire human population with appreciably fewer iPSC lines than an HLA-matched haplobank, with the off-the-shelf convenience of a standard allogeneic approach. Yet, this method is in its early stages, and thus, far from clinical use. The repeated gene editing is also associated with safety risks and any cell products will have to be carefully assessed for off-target effects.
Ongoing Clinical Trials involving Allogeneic iPSCs
The majority of the ongoing allogeneic iPSC-based clinical trials focus on ophthalmic diseases. The second most common focus is neurological disorders, while cardiovascular diseases take the third position. Together, these three indications account for more than half (approximately 52%) of iPSC-based clinical studies.
Despite the “hype” around allogeneic iPSC studies in recent years, the technology has yet to reach the clinical investigational phase on a broader scale. Only time will reveal if allogeneic iPSC technology will be able to overcome its challenges, which include carcinogenicity, lack of in situ integration, genomic instability, and immunological rejection, to ultimately make its way into routine clinical use.
Companies that are exploring the development of allogenic iPSC-derived cell therapeutics include Avery Therapeutics, Bluerock Therapeutics (owned by Bayer), CellOrigin Biotech and Qilu Pharmaceutical, Cellectis in partnership with Cytovia Therapeutics, Century Therapeutics, Edigene, Editas Medicine, Eterna Therapeutics, Heartseed, Healios K.K., Hebecell, Implant Therapeutics, Ryne Biotechnology, Sana Biotechnology, SCG Cell Therapy, Shoreline Biosciences, and several others.
Also, both Cynata Therapeutics and Citius Pharmaceuticals are using iPSCs to generate nearly infinite quantities of other stem cell types. Specifically, both companies have technologies that allow them to generate iPSC-derived MSCs (i-MSCs).
You can details about these iPSC-based therapeutic programs, plus access a list of all known companies worldwide involved with the development of iPSC-derived therapeutics, at this page.
To learn more about the rapidly expanding market for iPSCs, view the “Global Induced Pluripotent Stem Cell (iPS Cell) Industry Report – Market Size, Trends, and Forecasts.”
