Sunday, November 25, 2018

Ingenious Immune System

Hello friends, today let's take a moment to appreciate how amazing is our immune system.

In our immune system, just like any regular car there are brakes in place to regulate it's working. Removing brakes can certainly enhance it's function which underlies the concept of immune check-point blockade.

Two such molecules on surface of T-cells are CTLA-4(Cytotoxic T-lymphocyte associated protein 4) and PD-1(Programmed cell death protein 1).

When CTLA-4 binds to it's ligand B7-1 and B7-2 which are often expressed in increased numbers on tumor cells it results in inhibition of T-cells and hence allowing tumor cells to evade apoptosis and survive.

Similarly when PD-1 binds to PD-L1on tumor cells inhibitory signals are relayed to T-cells.

In macrophages signal regulatory protein alpha mediates inhibitory signals on interacting with CD47 on tumor cells.

In NK-cells KIR2DL1(killer cell immunoglobulin like receptor 2DL1) mediates inhibitory signals.

So blocking these inhibitory signals by monoclonal antibodies can remove "brakes" on immune system ultimately enhancing their ability to kill tumor cells.

Approved antibodies include:
Anti CTLA-4-Ipilimumab
Anti PD-1-Nivolumab,Pembrolizumab
Anti PD-L1-Avelumab,Durvalumab

Kirtan Patolia

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