Is Banking of HLA-typed iPS Cell Lines for Cell-Based Therapy Practical, Sustainable and Commercially Feasible?

Written by Norio Nakatsuji

The first pilot clinical study of cell-based therapy using human induced pluripotent stem cell (iPSC) has started in Japan, and banking of HLA-typed iPSC lines is proposed for practical application of the iPSC-based therapy.

The first pilot clinical study of cell-based therapy using human induced pluripotent stem cell (iPSC) lines derived from patients has started in Kobe, Japan, and it is attracting large attention. Such strategy of using patient-derived iPSC lines, however, requires long period and high cost, perhaps around one year and a half million USD, and may not allow practical and sustainable therapy for many patients. An alternative strategy is banking of HLA-typed iPSC lines, recently proposed by several stem cell scientists.

It is definitely different, however, to consider technical feasibility and practical/commercial feasibility. For example, a research-grade iPSC line can be derived at a cost of 10-20 thousand USD, but a clinical-grade line may cost 0.8-1.0 million USD (as mentioned in the following paper). Now, a timely paper has been published, which examined the question whether such HLA-typed banking for clinical application is practical, sustainable and commercially feasible (C. A. Bravery, Do HLA-typed cellular therapeutics based on induced pluripotent stem cells make commercial sense? Stem Cells and Development 2014, doi:10.1089/scd.2014.0136).

This paper is the first such examination of the practical feasibility of the proposed HLA-typed iPSC line banking and it merits careful reading. Its conclusion is, “Given the uncertainties and lack of clinical experience with iPSC-based CTP (cellular therapeutics) at this time, the financial costs and commercial risks do not appear to be acceptable.”

The author points out several important considerations. (1) Methods of reprogramming to produce iPSC lines are still improving and there is no standard method established. (2) Assurance of the quality equivalence between iPSC lines and banking facilities is very difficult. (3) Immunological rejection may be reduced but still occur even with matching of a few HLA loci. (4) Banking of iPSC lines is not enough, but in practice, CTP banking is needed by production of several to many types of clinical-grade differentiated cells, thus projecting enormous challenges. (5) Finally, commercial players that are indispensable for practical and sustainable therapy probably prefer exclusive cell lines but not those of public cell banking.

Then, what would be the alternative strategy for delivering pluripotent stem cell-based cell therapy at affordable cost? I have been considering an attractive possibility for several years, which is coincidentally mentioned in this paper. It is to develop reliable methods for induction of the antigen-specific (cell line-specific) immunological tolerance by manipulation of regulative T cells, dendritic cells, etc.

In any cases, for construction of the scientifically and economically sound strategy, it is acutely necessary to gather wisdom by extensive and deep discussion among stem cell scientists, immunologists, clinicians, industry, regulators and policy makers.