Oct 1, 2018

Immunotherapy could be the "fourth pillar" of cancer treatments

Jim Allison. Photo courtesy of the University of Texas MD Anderson Cancer Center

Jim Allison, today's winner of the first Nobel prize for cancer therapy along with Kyoto University's Tasuku Honjo, says he expects immunotherapy to be the "fourth pillar" in cancer treatments, along with radiation, chemotherapy and other gene-targeting treatments.

Why it matters: Immunotherapy treatments for cancer had a slow start, but persistent research has led to breakthroughs in the technology. Allison is responsible for developing the checkpoint blockade approach, which locates and blocks a key protein (CTLA-4) so that the immune system can attack cancer cells.

The backdrop: Allison, whose work at UC-Berkeley led to the discovery of CTLA-4, says early research had failures because they "started with insufficient knowledge."

  • Allison said he discovered the protein because he "wanted to know how T-cells work," and eventually tested the technique on a patient with advanced melanoma. That patient has since remained cancer-free more than 14 years.
  • His discovery led to the first drug that binds the CTLA-4 protein, called ipilimumab (or Yervoy), approved by the Food and Drug Administration in 2011. Yervoy's use has been extended to target other cancers, including some types of lung, kidney, bladder and Hodgkin lymphoma.

Meanwhile, the other prize recipient, Honjo, discovered a protein in 1992 that also inhibits the immune system, called PD-1. In 2015, the FDA approved anti-PD-1 therapy for malignant melanoma, and later extended the approval to non-small-cell lung, gastric and several other cancers. Two PD-1 therapies include pembrolizumab (or Keytruda) and nivolumab (or Opdivo).

  • Allison says that in many cases, the combination of both CTLA-4 and PD-1 offers a more potent punch. The success rate went from about 20% for CTLA-4 by itself to 60% when both were taken together.

What they're saying:

“By stimulating the ability of our immune system to attack tumor cells, this year’s Nobel Prize laureates have established an entirely new principle for cancer therapy.”
— Nobel Assembly of Karolinska Institute in Stockholm announced
"Jim’s work illuminates the fundamental mechanisms governing how cancers evade the immune system and has led to a new class of drugs that are producing Lazarus results for patients suffering from cancer. His science and passion has saved and will continue to save many lives."
— Ronald DePinho, professor and past president, MD Anderson, tells Axios

What's next: Allison says research in the fundamentals of how the immune system works, how immunotherapy can be combined and how to mitigate side effects is still needed.

What to watch:

  • The success rate varies among cancers — for instance, melanoma has 60% curative rate from immunotherapy, which is higher than many others.
  • One theory, he says, is that immunotherapy appears to work best with cancers with a high level of mutations (like melanoma, which can have up to 3,000 mutations/cell) to be targeted by T-cells.
  • While he says scientists tend to avoid the term "cancer cure," Allison believes further research will show immunotherapy used in combination with the three other pillars "will be curative to a lot of patients" and adds that "there is hope for cancer patients."

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