The 2018 Nobel Prize in Physiology or Medicine was announced on October 1, a day of national celebration, one of the winners is James Allison, professor and Chairman of the Immunology Department at the University of Texas Andson Cancer Center. Professor Allison found that on the surface of immune cells, a protein called CTLA-4 acts as a“Molecular brake,” stopping the immune response; if CTLA-4 is inhibited, it causes T cells to multiply and attack tumor cells, for which he won a Nobel Prize.
In fact, in the field of organ transplantation, there is a new type of immunosuppressant closely related to CTLA-4 molecule, it was approved by the FDA in 2011 to prevent acute rejection in adult kidney transplant patients. It’s called Belatacept (Nulojix) .
Beckham is a selective t-cell costimulatory signal blocker, consisting of CTLA4 fused to the FC domain of a human immunoglobulin antibody, which effectively blocks the binding of CD28 to B 7 molecules, leading to the development of a novel anti-CD28 antibody, it acts as a“Molecular brake”, inhibiting the activation of T cells and protecting the transplanted organ from rejection. In addition, it does not inhibit the body’s immune response to other viruses (BK virus, etc.) or pathogens, so it can reduce the risk of infection after kidney transplantation compared with other immunosuppressants.
As a new type of immunosuppressant, Beckham is similar to cyclosporine, but it is superior to cyclosporine in protecting long-term graft kidney function, this may be related to its lower nephrotoxicity. Two multicenter randomized controlled clinical studies evaluated the efficacy and safety of the use of scallops in kidney transplant patients, in the scallop and cyclosporine groups, and in the control group, the acute rejection rate was 24.0% and 22.8% , and the graft loss rate was 2.2% and 3.6% , respectively. The glomerular filtration rate at 1 year was significantly higher in the scallop group than in the cyclosporine group. The 5-year and 7-year follow-up results of the BENEFIT-EXT trial also confirmed better allograft survival and sustained improvement in renal function with scallops than with cyclosporine.
However, Ogai is not perfect. First, it has some serious adverse reactions, such as Lymphoproliferative disorders and progressive multifocal leukoencephalopathy after organ transplantation. Second, at present, Beckham is being studied as an alternative immunosuppressant, but large-scale, long-term follow-up data are lacking, and Ogai is not yet available in the Chinese market, domestic kidney transplant patients have not yet had the opportunity to use it.
Text, editing | Jina Wang, photography | G.T.
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