Immunotherapy is the art of taking the power of the immune system and diverting it to kill cancer cells. Up to about, you know, 20 years ago, the word cure was almost forbidden in the oncology dictionary if you wish. And in the last 10 years this particular armamentarium of immunotherapy is giving us hope.
However, it’s still a minority of cancers in which we’re seeing immunotherapy work. We’ve made impressive progress, but you know there’s much greater distance yet to go.
Amgen has really been an innovator in the area of immunotherapy with our BiTE molecules. And we have now a whole portfolio of BiTE molecules that we’re advancing through clinical studies. But in addition to that, we have a whole other approach trying to identify novel checkpoint molecules that are governing the immune response to cancer.
So immune cells have both gas pedals and brakes that control their function. And the brakes, in particular, prevent the immune cells from attacking our own tissues—and cancer, of course, arises from our own tissues.
One of these brakes is known as CTLA4, and what’s fascinating is one of the current checkpoint drugs attacks the CTLA4 protein. Now we know from human genetics that people with mutations in CTLA4 have a predisposition to get autoimmune diseases.
So in autoimmunity, the immune system become hyperreactive. Immune cells like T cells start attacking your own tissue. If we can identify those pathways, we actually can redirect the immune cells to attack cancer. So we actually now explore human genetics to try to identify pathways.
And so we turned to our colleagues at deCODE Genetics, and we asked them, Gee can you identify for us regions in the genome that contain genes that predispose to autoimmune diseases, say like rheumatoid arthritis. And they said sure, and they gave us a list of genomic regions. And Wenjun Ouyang went hunting in those genomic neighborhoods, and he came up with some candidate genes that he thought might be responsible for this effect that deCODE was seeing.
So identifying a gene or pathway through human genetics is just really the first step of innovation, right? Because a lot of time, we don’t know the function of that gene or that pathway.
We don’t know where that protein is in the cell, we don’t know what that protein does. These are all things we need to figure out.
In the last five years we witnessed a revolution in the technology tools that we have now available to study biology.
This revolution includes tools like CRISPR which allows us to edit in and out very efficiently genes into cells. It includes viral vectors which we can put into cells and regulate genes up or down at will.
We do single cell RNA seq on all these immune cells in a tumor to identify the genes that they are expressing. And if we find something that looks like a brake being expressed in those cells, then we can make a medicine that targets that brake to essentially release it. And so that’s another approach that Wenjun is taking that’s looking very, very promising.
By closely working with deCODE, we are working on some very novel genes and novel pathways. So therefore being able to perform this cutting-edge science and thinking about every day how we can translate this novel mechanism and pathways into immunotherapy is exciting everyone on my team.
It’s perhaps ironic, but when I came to Amgen, I was expecting that I was going to be, you know, the disruptive influence, coming from academia. And what I found very quickly was I was actually more conservative than my coworkers, and I was shocked at the audacity of what people were trying to do.
We can’t solve these problems by incrementalism, and it’s going to take bold, visionary strokes.
Three years ago, I lost my brother to cancer. He actually entered a phase 1 clinical trial for one of the therapies that’s now on the market, and he didn’t respond.
So when I look at the work that we’re talking about today, we can potentially save thousands and thousands of other people’s brothers and uncles and sisters and mothers and daughters and sons over the next generation. That’s a very powerful feeling.