CTLA4-Ig fusion proteins contain the extracellular domain of CTLA-4 and Fc fragment of human IgG antibody.
A fusion protein comprising the extracellular domain of CTLA4 and a modified CH2-CH3 domain of IgG (16) (
CTLA4-Ig) has been shown to inhibit T-cell-dependent antibody responses; prolong transplanted organ survival; and induce long-term donor-specific tolerance in transplants of heart, kidney, bone, and skin (17-19).
Unlike rituximab and belimumab, which target B cells, abatacept (
CTLA4-Ig) inhibits T-cell costimulation.
Also in Maxygen's pipeline are a new Factor VIIa product candidate for the treatment of hemophilia and new
CTLA4-Ig product candidates for the treatment of rheumatoid arthritis.
The two that received only
CTLA4-Ig rejected the new organ within a month.
Heitger, "
CTLA4-Ig preserves thymus-derived T regulatory cells," Transplantation, vol.
Separately, Repligen announced that is has received a Notice of Allowance from the United States Patent and Trademark Office on a patent which claims the use of
CTLA4-Ig for treatment of rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosis.
The Role of CD80 Upregulation and
CTLA4-Ig to Prevent Proteinuria.
Repligen Corporation (Needham, MA; 781-449-9560) announced that it has acquired rights to a United States patent application broadly claiming the use of
CTLA4-Ig in immune-based diseases and organ transplantation.
Two studies demonstrated that treatment with
CTLA4-Ig, which can reduce self-reactive T cell activation and liver inflammation significantly, could obviously reduce the level of portal inflammation and biliary cell damage in the mouse model [11, 12].
The approval of LEA29Y (belatacept) as a
CTLA4-Ig protein for use in renal allotransplantation brought costimulation blockade to the clinic in the early 2000s [26,27].