World-first NZ study: How new gene editing tech can boost smart cancer drugs
Itās one of the biggest breakthroughs of our lifetime: clever drugs trained to harness the power of our own immune system and unleash it against
cancer cells as they attack us.
But, while immunotherapies like the well-known
Keytruda are
revolutionising cancer treatment, theyāre still only effective in about a third of patients - and scientists donāt yet know why.
āWhen immunotherapies are successful, theyāre super-successful - but thereās still a massive 70 per cent of patients who donāt respond to therapy,ā said Dr Hilary Sheppard of the University of Aucklandās School of Biological Sciences.
To help solve that mystery, her team plan to turn to another of our generationās biggest game-changers - Crispr Cas-9
gene editing - to deeper explore an immune cell pathway that most immunotherapies target.
Their new study, just awarded a $940,000 grant from the Marsden Fund, could ultimately help improve the effectiveness of these drugs - with implications that reach well beyond cancer treatment.
āWhat weāre interested in is this particular pathway, called the PD-1 pathway, thatās activated in any situation of chronic immune stimulation - whether thatās cancer, chronic infection, or autoimmunity,ā Sheppard explained.
āIf youāre healthy, your immune system can kill rogue cancer cells.
āBut cancer cells can also fight back using a suppressive mechanism that we can think of as a lock and key system - that is, locks on the cancer cell, called ligands, that engage with keys on the immune cells, called receptors.ā
When the lock and key are engaged, it effectively dampens down the immune system - and the roving hunter-killer T-cells within it - as it tries to stamp out cancer cells spreading in our bodies.
Within the PD-1 pathway, cancer patients have been found to have varying levels of a key molecule - and just how these different levels affect treatment outcomes, or establish lasting immunity, remains a mystery.
āWhile youād think that patients whose PD-1 pathways are very active would respond very well to immunotherapy drugs, that isnāt always the case,ā Sheppard said.
āThen, in other patients where that pathway doesnāt seem to be as active, the immunotherapy drugs can work - so thereās a lot we donāt understand about it.ā
This is where Sheppard and her team planned to employ Crispr Cas-9 ā a system that can be used like molecular scissors to splice and snip genes, or insert new ones - on in-vitro samples in the lab.
āUsing the standard techniques that we employ to understand gene expression, we either knock out a gene completely, or we over-express it at wildly high levels, way beyond physiological levels,ā she said.
In this case, the team didnāt want to edit out the troublesome pathway completely, as this could cause adverse effects like auto-immunity.
āRather, what weāre trying to do is fine-tune the system to find that sweet spot thatās going to allow for the specifically targeted killing of the cancer without having any adverse effects.ā
As far as Sheppard was aware, this sort of editing had never been performed on endogenous genes before - nor in human T-cells.
But more exciting was the studyās potential to unlock major new insights into a vast range of diseases and disorders involving our immune system - all of which could advance new clinical treatments.
āUnderstanding this pathway has implications for multiple immune conditions.ā
Can gene editing help unlock the power of ground-breaking immunotherapy cancer drugs?
www.nzherald.co.nz
Reading online, there are some amazing advancing being made with immunotherapies and genetherapies. While the science is pretty much only in itās infancy, itās hoped that a number of cancers currently dealt with by chemotherapy would instead would use these new treatments which are far more tolerated than chemo.
The Malaghan Institute in Wellington are currently running trials on CAR T-cell treatments for some cancers.
www.malaghan.org.nz
