Checkpoint inhibitors have taken the cancer drug market by storm.
In fact, the #1 best-selling drugs by global sales is Keytruda, followed by #3, Opdivo.
They both target checkpoints in T-cells, the PD-1.
But are they as exciting and promising as many believe today?
For one thing, checkpoint inhibitors have demonstrated very low efficacy.
They are best-selling, but they are rarely effective when used alone.
They are used as additional drugs, such as chemotherapy.
Why do they have low efficacy?
Because they only work on T cells’ break, while ignoring the rest.
Checkpoint inhibitors work by “inhibiting the inhibition.”
Let’s say you have a car. That’s the analogy for the cancer-killing T cell.
The car needs to roll all the way to the end and run over cancer.
But in cancer patients, the car is barely moving.
To get the car moving, checkpoint inhibitors remove the brake.
The car indeed starts to roll slowly.
On a flat landscape, it rolls all the way down the alley and kills cancer.
But on a bumpy road? The car gets quickly stuck.
Cancer cells and Myeloid-derived suppressor cell in cancer patients
secrete molecules that suppress immune cells’ activities.
Inhibiting the brake alone cannot overcome this challenge.
That is why checkpoint inhibitors, inherently, have low efficacy.
Another problem is that… a car without a brake is a dangerous thing.
Nature endowed human T cells with checkpoints because they are important.
They prevent them from over-shooting or attacking self-cells.
Now, in an effort to kill cancer cells,
checkpoint inhibitors are inhibiting the brake.
Not only is this unnatural, but it can also lead to side effects
such as autoimmune symptoms.