The Future of Cell Therapeutics for Autoimmune Diseases

Gene therapy and cell therapy have seen major developments and approvals as cancer treatment, and according to Biju Parekkadan, PhD, it is only a matter of time before these developments start to happen within the autoimmune community. Dr Parekkadan, professor of biomedical engineering at Rutgers University in Piscataway, New Jersey, presented on the use of human cells and cellular therapeutics at the Interdisciplinary Autoimmune Summit 2020 virtual meeting.

Essentially, “the goal for genetic engineering is to reboot, redirect, or re-educate, the immune system,” said Dr Parekkadan. He reviewed three different cells types with three different mechanisms of action for cell therapy:

• Hematopoietic stem cells (HSC)
• Mesenchymal stromal cells (MSC)
• Regulatory T cells (Tregs)

HSC are derived from bone marrow transplants and include all cells in the blood. This method essentially reboots the immune system by transplanting a blood sample to reconstitute the immune system and diversity as well as minimize the attack against cell tissue. While bone marrow transplants have shown some promise in multiple sclerosis, rheumatoid arthritis, and lupus, there are significant mortality and morbidity risks.

MSC is also from bone marrow and is fibroblastic in nature, said Dr Parekkadan. It was evaluated as a possible immunomodulating treatment and is developed using cells from a donor. The cells are expanded outside the body and administered intravenously to the patient with Graft versus host disease, for example. In a case study, a child with Graft versus host disease treated with 2 doses of MSC showed some reduction in the adverse event.

Unfortunately, one aspect of this therapy that is hindering its approval for systemic use is the lack of bioavailability of the cells. Once infused intravenously, the measured amount of MSC in the blood in humans drops. “After 6 hours, there are no stem cells in the patients, which is a sign that these cells are getting destroyed,” he said. There has been some interest in developing an external ex vivo cell device to control the duration and amount exposure of MSC.  

T cells are innately involved in the suppression of autoimmune reactions and can be identified by surface markers. Studies in lupus and type 1 diabetes have demonstrated the safety with and good bioavailability of purified T cells, with cells persisting months after infusion.

According to Dr Parekkadan, there is hope among scientists working in synthetic biology in the concept of a universal platform of human cells. “The idea is that these cells can be recreated and induced into pluripotent stem cells that can be modified and universally sourced for any of these options,” he said. The possibility of gene editing and combined with the number of cell populations that induced pluripotent stem cells can produce is outstanding, said Dr Parekkadan. It is another 30 years away, but Dr Parekkadan noted that this could be a possible renewable source for cellular medicine.

Another idea under development is creating chimeric antigen receptor T (CAR-T) cells that can sense certain diseases or biomarkers and trigger a cellular response. CAR-T cells used in cancer treatment are now being developed with antigen-specific Tregs to harness the background and provide the right antigen to target the disease. This is also being evaluated in colitis and multiple sclerosis and already demonstrated efficacy in murine models, said Dr Parekkadan.

Other approaches in the pipeline that Dr Parekkadan reviewed included developing a genetic switch based on physiological responses, such as circadian rhythm, immunosensors trigged by local inflammatory response to secreted protein, and genetically encoded oscillators.

One of the biggest challenges for these therapies is the manufacturing, said Dr Parekkadan. There are some new developments that are being tested to see if these cells can be produced using automated processes on a mass scale to meet the needs of large patient populations and reduce cost.

For more coverage of IAS 2020, visit the newsroom.

—Melissa Weiss

Reference

Parekkadan B. Emerging cell therapeutics for use in autoimmune diseases. Presented virtually at: Interdisciplinary Autoimmune Summit 2020; July 12, 2020.