By Betty Zhang
Current CAR T cell therapeutics cannot simply be bought off a pharmacy shelf. Each treatment is tailored specifically to the patient - retrieving and modifying their own T cells to recognise and attack cancer cells before introduction into the immune system.
This not only requires time that delays treatment timelines but also reduces the accessibility of such treatments.
Current reality for CAR-T therapy
Manufacturing times for CAR-T cells currently take up to 4 weeks, which means that only patients must be in a stable condition to possibly benefit from treatment. Patients who have already undergone extensive chemotherapy and treatment that have compromised their immune system may also not have enough T cells to be collected for modification & infusion.
Due to individual differences between patients’ cells, the end product will also be variable. Current autologous treatments have significant logistical needs from the collection of patient T cells, to adequate manufacturing facilities and treatment procedures that are challenging to operate at scale.
+ exciting Melbourne based research
The next frontier of CAR-T cell advancement is to create allogeneic therapies for patients that are pre-made from healthy donor cells. The promise of off-the-shelf therapies is to reduce burden in delivering this treatment and to allow patients with more aggressive disease to benefit. There is little doubt that increases in scalability & availability of such treatments will also reduce cost to patients and healthcare systems. More info
Healthy cells from donors called induced pluripotent stem cells (iPSCs) have the potential to be reprogrammed into immune cell types such as T cells for modification and delivery as living drugs.
This is an exciting field of research and there have been significant progress made in both academia and industry. Based in Melbourne, Victoria, Australian company Cartherics have been working to develop new off the shelf immune cell therapies for cancer. Nicholas Boyd, a research scientist at Cartherics, is excited to deliver “immunotherapy for the masses” through his work.
Nicholas has worked to develop platforms and technologies to upscale manufacturing of iPSC-derived T cells. By developing a simple method that could be adaptable from a small-scale lab bench to a large-scale manufacturer, he hopes to reduce the cost of generating T cells for treatment from one stem cell source.
Nicholas has also been working with a team to develop CAR-NK therapy for solid tumours which overcomes risks of graft versus host disease associated with T cell therapies while maintaining cancer cell killing functions. Ovarian cancer has been another focus of Cartherics, a solid tumour with one of the biggest needs for advanced therapies such as stem cell based immunotherapy.
+ applications
With great promise comes great challenges and important considerations. Unlike autologous therapies, allogenic immune cells may cause life-threatening graft-versus-host-disease (GVHD) as they may recognise and attack the body’s healthy cells. Secondly, attack from the host immune system may eliminate and limit the antitumor activity of allogeneic immune cells. Strategies based on the selection of cell source and genetic modification are being used to mitigate these risks.
CAR T cells made from umbilical cord blood are associated with reduced incidence and severity of GVHD as they have an unique antigen-naive status. iPSCs which have an unlimited capacity to self-renew can also be used to create cell banks with common HLA haplotypes. Gene editing techniques to eliminate T cell receptors at the surface of CAR T cells could also be used to avoid allorejection, supported by positive preliminary clinical results. More info.
In the clinical setting, allogeneic CAR T cells offer the opportunity to treat relapsed or refractory cancers with a readily available product. For diseases with poor prognosis, CAR T cells may also be deployed as frontline treatment in the future or used in combination with other therapeutics. For the treatment of solid tumours, conventional CAR T cell therapies have demonstrated little success, yet allogeneic CAR T cells have the capacity for further genetic modifications that may optimise their use.
Comparison between autologous and allogeneic CAR T cells
Happy reading!
