Cell Therapy on Demand

Over the course of the last decade, cell therapies have changed the cancer treatment landscape. Though autologous therapies, which require patients to undergo apheresis (immune cell harvesting), can be used to address patient needs, they are complex and time-consuming, especially when used for very ill patients. Having cell therapy products available when a patient needs them, without having to harvest and engineer a patient’s own cells, would eliminate some of the complexity and speed up the time to treatment. The sooner a patient can be treated, the higher the likelihood of a better outcome for them.

These “off-the-shelf” allogeneic cell therapy products could be manufactured in bulk and given to a broad number of patients on demand. This approach could address the two major manufacturing challenges current autologous therapies face: no inventory and variable quality of starting material. Because autologous therapies use a patient’s own cells, manufacturing cannot start until the cells are collected from the patient and delivered to the manufacturing site. The clock starts ticking as soon as the cells leave the patient, so any last-minute changes to the collection or delivery process can greatly impact manufacturing planning.
 
Patient populations, of course, are not homogenous – individuals will vary in age, immune status, and treatment history. This means that the quality of starting materials, like the patients themselves, will differ – making process validation and standardization difficult. When treatment can shift to allogeneic therapies, these challenges can be overcome. Cells could be manufactured, frozen, and stored in multiple doses ready for use, making process standardization a reality. Every patient would receive cells of the same type with defined characteristics.
 
But developing allogeneic therapies has proved difficult. The cells must not be rejected by the patient’s immune system before they can get to work and must not harm patients by attacking healthy tissues. These two considerations require different elements of cells to be genetically modified to prevent rejection and toxicity (graft-versus-host disease).

There are also many choices along the way – do you start with stem cell lines? Cord blood or healthy donor cells? Which editing tools do you use? Each option has advantages and disadvantages. One major factor that introduces variability is the cell source used. In my view, gene-editing stem cells is a flexible approach that minimizes batch-to-batch variation. At my company, we use a stem cell line created from a single donor. We then edit it and use it to make stem cell banks. This gives us control over our starting material so that each manufacturing run starts with the same cells. 

Though there are still challenges for the industry to examine and address, I’m excited by the progress being made across the industry in allogeneic therapies. These treatments hold tremendous potential for overcoming the main challenges of autologous treatments and can achieve the ultimate goal of being not only curative, but also mainstream for patients with cancer.