Cancer immunotherapy researchers earn prestigious Nobel for 2018

This year’s prize in Physiology or Medicine honors the discovery of cancer therapy by inhibition of negative immune regulation

By Rajaneesh K Gopinath

The Nobel Assembly at the Karolinska Institutet announced yesterday about their decision to jointly award James Allison, PhD, and Tasuku Honjo, MD, PhD for their separate pioneering works in “immune checkpoint” cancer therapy. Dr. Allison, also the recipient of the 2015 Lasker award is currently the chair of the department of immunology at the University of Texas MD Anderson Cancer Center in Houston while Dr. Honjo is a professor of immunology and genomic medicine at Kyoto University in Japan.

Although the utilization of our body’s own immune cells to counter cancer progression had been conceptualized much earlier, it was considered a fantasy until the seminal works of these scientists. In the mid 1990s, Dr. Allison’s research demonstrated that cytotoxic T-lymphocyte antigen 4 (CTLA-4), a receptor molecule expressed on T cells, acts as a brake to prevent immune response. CTLA-4 was originally identified by the French immunologists Pierre Golstein and colleagues in the late 1980s and it was hoped to be used to treat autoimmune diseases. However, Dr. Allison tested whether tumors could be targeted by immune cells by releasing the brakes applied by CTL-4. This led to the development of a monoclonal antibody against CTLA-4 that resulted in tumor regression in mice. The antibody Ipilimumab (trade name Yervoy^TM, Bristol-Myers Squibb, Princeton, NJ), was approved by the USFDA in 2011 for the successful treatment for advanced-stage melanoma.

On the other hand, in 1992, Dr. Honjo and coworkers discovered a new protein, Programmed Death 1 (PD-1) on T cells, another molecule that could act as a brake in the activation of the immune system by binding to PD-L1 on other cells. In fact, many cancers fooled the immune system by expressing PD-L1 on their surfaces. Blocking PD-1 with antibodies effectively reduced the size of tumors. This led to the development and approval of anti-PD-1 drugs like Keytruda (Merck & Co.) and Opdivo (Bristol-Myers Squibb) in 2014. Although met with initial skepticism over possible side effects, cancer immunotherapy has rapidly risen to the status of an effective therapeutic strategy against cancer in a short time making this award a well-deserved recognition for excellence in science.

References

1. https://www.nobelprize.org/prizes/medicine/2018/press-release/
2. https://www.sciencemag.org/news/2018/10/cancer-immunotherapy-pioneers-win-medicine-nobel

Note: Stay tuned to Geneonline for our special article on these Nobel laureates.

Author

Rajaneesh K. Gopinath