CTLA4-Ig

CTLA4-Ig

A fusion protein specific for the B7 surface receptor on T cells that has been shown to be capable of persuading T cells to recognize severely mismatched allogeneic transplanted organs as ‘self’ even in the absence of immunosuppressive drugs. T cell activation requires two signals—a T cell-receptor-mediated signal and a co-stimulatory signal. Co-stimulation involves the B7 receptor. This fusion protein blocks co-stimulation and prevents T cells from mounting a rejection attack.
References in periodicals archive ?
Chi220 has been shown to extend allogenic islet survival time to more than 200 days in combination with belatacept (CTLA4-Ig) in MHC-mismatched rhesus macaques [75].
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.
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].