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.

Go to the profile of Dr Alison Halliday
Jan 31, 2018

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.

Go to the profile of Dr Alison Halliday

Dr Alison Halliday

Community Manager, Nature Research

Molecular Biologist turned freelance science communicator, with 10 year's experience at Cancer Research UK.


Go to the profile of David Hicks
David Hicks about 1 year ago


Cancer is a coalescence (1), of a chance mutation (2,) and (3), a cellular specific (4), chronic (5), disease (6), or mutation (7).

  1.  The mutation and the chronic effect must both act at the same time.
  2. Chance mutations are known to randomly appear for no known reason. Environmental exposure can increase the risk of mutation. Chronic exposure, including smoking, can replace the role of chronic disease.
  3. Neither a chance mutation nor a chronic disease on their own, can cause cancer. A familial mutation will require a cellular specific injury.
  4. Cell specificity, which is the cell type that initiates the chronic disease, dictates which cell type becomes cancerous.
  5. Chronicity increases the possibility of the “chance” mutation by multiplying the possibility.
  6. A chronic disease in the alpha cell lineage, (from the endoderm); this will cover the majority of cancers; will have inhibited apoptosis or deleted p53 which then allows the chance mutation to survive. A chronic disease in the beta cell lineage, (from the mesoderm), will have neither an inhibited or activated apoptosis, it will have an altered autophagy, which will also allow a mutation to survive. These chronic diseases can allow sporadic cancers to form.
  7. A pre-mutated gene is required for genetic familial cancers. The mutation stalls pre-cell cycle pathways.
  • Note: When a cancer cell metastasises and travels elsewhere in the body, it does not pass on its “cancer” properties to other different types of cell. The stalled biological changes that occur in the initiating disease, such as growth factors, cytokines, etc. are spread throughout the body in the bloodstream. The combination of these changes is specific to the initiating cell type in the chronic disease, designed to allow only that type of cell to proliferate. So, if a prostate cancer cell metastasises to bone, it does not cause bone cancer, it remains as prostate cancer, and is fed all the required biological changes required for prostate cell growth; through the blood stream.                
  • Coalescence: To come together and form one whole.
  • Author:  David Hicks.                                Email: