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Saturday, June 03, 2017

Checkpoint inhibitors

Checkpoint hero 

The band got a raucous approval, James Allison grinned after giving his harmonica a rest,
Another band 
Another evening 

This was a band with a difference, its players were all senior researchers in cancer and the audience was from ASCO American society of clinical oncology annual meet where more than 40000 oncologists’ immunologists and clinicians gathered in Chicago year after year to procrastinate plans to fight their common enemy cancer!
Immunology was always the elusive bait to success in cancer treatment,
It’s Holy Grail almost,
if only one could muster the body’s defence mechanism to fight its abnormally growing cells no more need to be done ,something which it does routinely for any foreign cells but then there was the catch
What can one do to make it do what it needed to!
The B and T cells are the two most important immunological soldiers of the human body,
Some scoffed at them
One went to even say the B and T are the starting and ending alphabets of the word Bullshit!
But James ignored these jibes and went on his work with a determination unsurpassed.
The need of the hour was to find that elusive something that activated a T cell!
And he did find out the driving engine that could activate a T cell
Its antigen alone was not enough but needed to find out other stimulatory molecules which he did after painstaking research as a CD28 molecule which was needed to spur on a virgin T cell to action
Interestingly at this time other researchers had found that there was another molecule bearing uncanny resemblance to CD28 in its B7 ligand and suggested that this was another co stimulatory molecule needed to sustain the T cell activation but James and his team begged to differ,
They felt instead of being a stimulant this molecule was an inhibitor or rather if CD28 is an accelerator CTLA4 was the brake so if someone could take off the brake the T cell would start doing its job well
And the team proved it to be so
Allison started thinking if the T cell could be allowed to work unabated it would destroy the cancer cells and here it is not based on the type of tumour but for all tumours the same principle can be used.
It took a long ten years for Allison who was not a physician but a core scientist to associate with a pharmaceutical firm to produce an antibody against the inhibitor and go through the stringent clinical trials in association with leading medical centres and finally get approval for iplimumab the first success story in immunotherapy in cancer in Malignant melanoma and which has now become part of its protocol of management saving many who would have had to die but for it
And today two other drugs which are programmed death inhibitor and programmed death ligand inhibitors Nivolumab and Pembrolizmab is already being used
Immunotherapy has now gone on in detection of more check point inhibitors in lung, urothelial , renal malignancies and the fire lit by Allison is making a difference .
So it was a cheerful Allison who placed his harmonica on the floor after the loud applause from his enlightened audience
He now is in the Times magazine’s list of 100 most influential people in 2017

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