Meet the men behind the framework

Find out more about men behind the cancer-immune setpoint and the story of how they came up with their big idea.
Meet the men behind the framework

Ira Mellman, PhD, is a member of the National Academy of Sciences and former Yale Professor. Dan Chen, MD, PhD, is an oncologist and former Howard Hughes Medical Institute Associate who ran the Stanford University Cancer Centre’s metastatic melanoma clinic.

Both leading authorities on the human immue system, they left stellar academic careers to join Genentech, part of the Roche Group.

Ira Mellman never intended to be a scientist when he was growing up, he was instead intent on a career in music – until an undergraduate biology course changed his mind. Following this with a PhD at Yale then postdoctoral work at Rockefeller University, he then returned to Yale where he ultimately became Cancer Center Director.

His decision to leave academia was motivated by events in his personal life – seeing two of his children cope with a chronic inflammatory disease, as well as losing friends to cancer.

“To see that, and then being presented with the opportunity of moving to what’s the best place on earth to do drug discovery – I don’t know if it’s a moral obligation to act on that,” explains Mellman. “But it certainly was a motivating force for me.”

Dan Chen’s route into science follows in the footsteps of his parents who emigrated to the USA to pursue careers in physics. He studied at MIT, USC and Stanford, attaining degrees in molecular biology, immunology and medicine. Following a medical oncology fellowship, he carried out postdoctoral research in a prestigious immunology lab.

The combination of his MD and PhD left Chen perfectly positioned to bridge the gap between the lab and the clinic – caring for patients while also studying their disease.

“It’s difficult to imagine anything more motivating,” Chen explains. “As a doctor, you go through this life and death battle with your patients. Back in the lab, you know you have to solve the cancer problem, to save these people. And there is the boundless hope that by understanding the underlying biology, that you’ll be able to come back with something better for them. That interplay really drives what you do as a scientist. You can see just how badly you need to make a breakthrough.”

At Genentech, Chen & Mellman forged a formidable partnership. Bouncing around their ideas in a local bar, they came up with what was the beginning of their groundbreaking concept - the cancer immune-setpoint framework, a unifying theory for how the human immune system interacts with cancer.

 “We had a fair amount to drink, and all of the loose concepts we had, they came together” reminisces Chen. “And so we really gelled. And that was a perfect moment of the two of us bringing together ideas, concepts, and and an over-arching figure. And that’s where it started.”

On cocktail napkins, they scribbled a circle of arrows containing seven circles, each with a drawing. This was the feedback loop of how the immune system recognises and kills a cancer cell. And so, the ‘cancer immunity cycle’ was born.

For the pair, their conceptual breakthrough is all about framing the biology as a tool that can help advance the development of cancer treatments.

“In any one patient, the cycle can fail at any one of a number of points. And if we can figure out which is the failure point for any one patient, then we can figure out what it is we have to do for that patient,” Mellman explains. “And that was it.”

Today, Chen & Mellman are working on more than 20 potential new medicines targeting four different steps of the cycle – and the field continues to evolve rapidly.

Chen and Mellman now need the wider community’s help to evolve the wider cancer-immune setpoint, which builds on the original cycle to create a unified theory of the state of a person's immune system. Please go to the framework and add your comments today.

This post is based on a longer article ‘Behind the Cycle’ – which you can read in full on the Roche website.