CTLA4Ig

CTLA4Ig, short for cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin, is a class of immunomodulatory fusion proteins used to dampen T cell–mediated immune responses. The two best-known clinical examples are abatacept and belatacept. They consist of the extracellular domain of CTLA-4 fused to the Fc portion of IgG1, and they bind to the costimulatory ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells.

Mechanism of action

CTLA4Ig interferes with the CD28–B7 costimulatory signal that is normally required for full T cell activation. By occupying CD80/CD86, these fusion proteins prevent adequate costimulation, reducing interleukin-2 production and T cell proliferation. This can lead to decreased T cell responses and may promote T cell anergy or tolerance, while potentially preserving some regulatory T cell functions.

Formulations and administration

Abatacept is approved for autoimmune diseases such as rheumatoid arthritis and is available in both intravenous infusion and subcutaneous injection forms. Dosing is typically weight-based for the IV form and may be scheduled weekly or every two weeks for the SC form, depending on indication. Belatacept is approved for prophylaxis of organ transplant rejection, administered intravenously on an induction schedule (and then on a maintenance schedule, usually monthly). Dosing and eligibility depend on the indication and patient factors.

Indications

Abatacept is used for rheumatoid arthritis in adults with inadequate response to TNF inhibitors, as well as for juvenile idiopathic arthritis and psoriatic arthritis. Belatacept is used to prevent kidney transplant rejection in eligible recipients.

Safety and cautions

CTLA4Ig therapy increases the risk of infections and malignancies. TB screening and vaccination considerations are important; live vaccines are generally contraindicated during treatment. Belatacept carries a specific risk of post-transplant lymphoproliferative disorder, particularly in EBV-seronegative recipients, so EBV status is commonly assessed before use.