According to the Alliance for Regenerative Medicine, more than 1300 clinical studies for regenerative medicine and advanced therapies, including autologous and allogeneic cell therapies, are ongoing (1). The cell therapy industry has achieved clinical success with the approval of autologous-based therapies including Novartis’ Kymriah®, Kite Pharma’s Tecartus™ and Yescarta®, and Bristol-Myers Squibb’s Abecma® (Celgene) and Breyanzi® (Juno Therapeutics). The challenges facing autologous cell therapies, including the acquisition logistics for patient cells, transport to a manufacturing location and back to the patient, and the high cost of manufacturing, are potential threats to the long-term success of the modality. Allogeneic-based therapies have the potential of overcoming some of these issues but face their own challenges. One of these obstacles is finding an appropriate source for the starting cellular material.
Induced pluripotent stem cells (iPSCs) are a viable option for use as starting material for cell therapies with several key features offering advantages to therapeutic innovators, clinicians, and patients. iPSCs can be expanded indefinitely, allowing for master and working cell banks to be established without loss of performance. Clonal lines can be thoroughly characterized. iPSCs can be cryopreserved and recovered very easily, which facilitates their handling compared to other cell types. They are also easily manipulated. In principle, iPSCs can be differentiated into various human cell types, making them an ideal universal cell source for therapies addressing a range of indications in the future.
From a developer’s perspective, the ability of iPSCs to self-renew at short division cycles allows for growing up large quantities of cells in a short amount of time and upscaling processes compared to other cells that run into senescence after a couple of passages. By nature of their pluripotency, iPSCs provide developers with starting material flexible to differentiate into the cell types they need, for instance cardiomyocytes, beta cells, NK cells, or specific types of neurons, to develop cell-based therapies for their targeted diseases. Additionally, fully documented and characterized clonal cell lines will help meet future regulatory requirements for clinical studies.
For patients and clinicians, many of these features imply that iPSCs can be distributed globally with proportionally less effort compared to the logistics necessary for autologous-based therapies. This can increase accessibility and potentially reduce costs.
A single cell line, fully qualified, documented and produced within a regulatory framework, could be a universal starting source for advanced therapies. For iPSCs to serve as a universal starting material, some obstacles need to be overcome. Although it may now be easy to generate iPSCs, the regulatory framework to produce the cells is still a challenge. Processes need to be conducted under cleanroom-compatible conditions with standardized protocols and qualified, validated analytical methods. Full documentation is required starting from sample acquisition from the donor, including donor eligibility and re-consent for commercial use of donated material. For clinical studies, embedding all of these items in a quality management system that meets international GMP guidelines will be critical. As some requirement differences exist between the US FDA and EMA, for example, related to donors, there is a need for alignment to facilitate a commercially feasible launch of a new therapy for global markets.
iPSCs have a bright future in the 21st century as the basis for novel cell therapies, from cell replacement therapies to treatments for cancers, and to helping larger populations instead of individual patients. Due to their robust, stable nature, iPSCs can be an ‘off-the-shelf’ source material for allogeneic cell therapies. Companies like Catalent manufacture iPSCs to be used directly or cryopreserved for future ‘off-the-shelf’ use. With their enormous potential to differentiate into several cell types, iPSCs could revolutionize regenerative medicine and immunotherapies, especially for indications where time for treatment is constrained or supply of donor cells is limited. Additionally, to improve the long-term success of cell therapies, it is important that the treatments are affordable for healthcare systems. iPSC-based allogeneic therapies could potentially open a new road to success for cell therapies, circumventing the current cost and logistical hurdles facing autologous-based therapies.
Reference:
(1) Alliance for Regenerative Medicine, “Regenerative Medicine in 2021, a Year of Firsts and Records, H1 2021”, https://alliancerm.org/sector-report/h1-2021-report/