DLBCL
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma, a fast-growing type of blood cancer. The medical need for DLBCL is significant due to its aggressive nature. Patients often require a combination of chemotherapy, immunotherapy, and sometimes radiation therapy to achieve remission. Despite advancements in treatment, there remains a need for improved therapies, especially for patients who relapse or do not respond to initial treatments.
CAR-T therapy is a recent advancement in the treatment of DLBCL and involves the modification of the patient’s own T cells to express chimeric antigen receptors (CARs) so that they specifically target and destroy lymphoma cells. Several CAR-T therapies have been approved for DLBCL, many of which target CD19 that is highly expressed on lymphoma cells. Such CAR-T treatments include axicabtagene ciloleucel (Yescarta), lisocabtagene maraleucel (Breyanzi), and tisagenlecleucel (Kymriah). These therapies are typically used as second- or third-line treatments. The fact that it takes several weeks to manufacture the CAR-Ts and that it comes at a very high cost limits its use and has led to intensive efforts to develop an off-the-shelf variant. In vivo CAR-T may be the solution.
B-cell dependent autoimmune disease
Autoimmune disease is often driven by B-cell dysfunction and the production of autoantibodies. Some of the most common B-cell dependent autoimmune diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and myasthenia gravis. There are emerging evidence that CAR-T therapy may have therapeutic effects in B-cell dependent autoimmune disease, and notably in SLE.
SLE
SLE is a chronic autoimmune disease that can affect multiple organ systems, including the skin, joints, kidneys, heart, lungs, and brain, and that is driven by autoreactive B-cells. It predominantly affects women and is characterized by periods of flare-ups and remission. Symptoms vary widely but commonly include fatigue, joint pain, skin rashes, and kidney problems. Standard of care for severe SLE involves a combination of treatments aimed at controlling inflammation and preventing organ damage, such as corticosteroids, immunosuppressants, and targeted therapies such as belimumab and rituximab. In vivo CAR-T therapy has the potential to become a future therapeutic option in SLE as well as in other B-cell dependent autoimmune diseases.