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CTLA-4Cytotoxic T Lymphocyte-Associated Antigen 4
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Ipilimumab is a competitive inhibitor of CTLA-4. CTLA-4 inhibits the binding of B7 and CD28, a co-stimulation signal, that activates T-cell and subsequent proliferation (3).
CTLA-4 and PD-1 trials advancing - interim analysis underway
Because many of these inhibitory markers are upregulated by T cells following activation or exhaustion, blocking the signal between the inhibitory ligand on the tumor surface and its receptor on the T cell (for example, between CTLA-4 and CD80/86, or PD-1 and PD-L1) will reactivate cells.
Receptors of CTLA-4 and PD-1 are expressed on T cells, whereas PD-L1 is expressed in many cell subtypes including tumor cells.
Frequencies of [CD4.sup.+] T cells expressing CD45RO, CD25, and CTLA-4 were significantly higher in the apical periodontitis lesions than in cells from the control samples (Fig.
He then created an antibody (a protein) that could bind with the CTLA-4 so that it no longer inhibited the T-Cell's function.
The results showed that PD-1, similar to CTLA-4, functions as a T-cell brake, but operates by a different mechanism (see Figure).
In an interview Monday, Allison, 70, said he wasn't trying to cure cancer but to understand how T cells work when, at the University of California, Berkeley, he was studying a protein named CTLA-4. He learned that the protein could put the brakes on T cells, creating what's called an immune "checkpoint." He then created an antibody that blocked the protein's action so the T cells could do their job.
Allison studied a known protein CTLA-4 that functions as a brake on the immune system.