CAR T therapy has had enormous impact in some areas of oncology, and notable efforts are underway to extend the success to additional forms of cancer. However, the use of engineered T cells may be even
more attractive for disorders other than cancer for several reasons.
This review analyses different opportunities and future directions.
First, for a cancer therapy to be effective, every neoplastic cell must be eliminated to avoid recurrence. By contrast, lowering the fibrotic burden in diseases characterized by fibrosis would likely have substantial clinical benefits. Additionally, B cell malignancies and other cancers can consist of multiple pounds of tumour cells, the lysis of which is a major contributor to cytokine release syndrome. In many
fibrotic indications, the number of pathogenic cells can be orders of magnitude fewer, thereby decreasing the risk of adverse effects such as cytokine release syndrome after cytotoxicity.
Because of the need to avoid recurrence and the enormous number of neoplastic cells, CAR T cells in cancer therapy are required to expand in vivo and to be long lasting, necessitating the use of viral transduction. This poses risks such as insertional mutagenesis, overactivation and the need for lymphodepletion.
Most non-cancer indications that could benefit from CAR T cell therapy do not have these requirements
and are able to use safer approaches, such as transient mRNA CAR T cells, that negate the safety risks associated with viral transduction. Such ‘transient’ CAR T cells could also be delivered in multiple doses over time to titrate the necessary effect while reducing side effects.
The appreciation of the power and potential for engineering the immune system to combat disease is among the most exciting advances in modern medicine. The challenge lies ahead of us to
extend these advances to a wider range of human afflictions and to use developing technologies to make these approaches safe, effective, widely available and affordable. The pace of advance is breathtaking, and early studies already predict the possibility of using CAR T cells or related products to treat autoimmune disorders, infections and the enormous unmet need of tissue fibrosis.
Strategies for developing effective immune therapies for non-oncologic disease may diverge from those used to treat cancer and may benefit from mRNA and nanodelivery advances. These are still the early days of the ‘immuno-revolution’ in medicine.