Understanding Immunotherapy Part 2: PD-1

By Amrita Bhatt, MRA Intern | 17 February 2016 | Science, Treatment

Now that we’ve provided a brief background on immunotherapy, it’s time to dive more deeply into the subject. In the second installment of this blog series, we’ll be examining PD-1, a protein that plays a crucial role in cancer’s ability to hide from our immune systems.

What is PD-1?
PD-1 is a protein found on certain immune cells, including a type of white blood cell known as a T cell. When PD-1 links up with its partner protein, PD-L1, a signal is sent to the T cells to shut down. Usually, this is used as a means to prevent the development of out-of-control immune activity that could lead to auto-immune disease. Unfortunately, the same PD-1/PD-L1 signal can be used by tumors to turn off T-cells and thereby help the tumors avoid being destroyed by the immune system.

What anti-PD-1 drugs are available now?
Two anti-PD-1 drugs have been approved by the FDA – Nivolumab (Opdivo®) and Pembrolizumab (Keytruda®). These drugs block PD-1 and free up the T cells to attack the cancer. Additionally, the combination therapy of Nivolumab and Ipilimumab (Yervoy®), an anti-CTLA4 drug, was approved just this past year.  First FDA-approved in melanoma, these anti-PD-1 treatments are also available for kidney and lung cancer patients, and the data are encouraging in a number of other cancers as well.

What type of anti-PD-1 research has MRA funded?
With melanoma serving as the lead for immunotherapy across various cancer types, research funded by MRA has played a pivotal role in advancing the field. Funding from an MRA Team Science Award to Drs. Drew Pardoll, Suzanne Topalian, and Lieping Chen at Johns Hopkins University provided some of the earliest observations on the role of PD-L1 as a potential biomarker in melanoma, lung, and prostate cancer patients. Correlating the expression of PD-L1 to treatment response has contributed to understanding its best use as a biomarker for cancer therapy.

Watch this video to learn more about research on immunotherapy that blocks the PD-1/PD-L1 pathway:

MRA has funded a number of studies on biomarkers for immunotherapy.  In partnership with the Lung Cancer Research Foundation and Lungevity, MRA-funded Young Investigator Dr. Lucia Jilaveanu is conducting research to identify biomarkers that relate to pembolizumab treatment in patients with metastatic brain disease. This partnership allows for powerful insight across cancers, as brain metastasis is a common feature of both melanoma and lung cancer. MRA is also currently funding the melanoma supplement of the SU2C-CRI Immunology Dream Team co-led by Drs. James Allison and Antoni Ribas. Their studies aim to identify biomarkers of response in patients treated with ipilimumab, nivolumab, and a combination of the two.

What’s Next?
With the potential to help combat not only melanoma, but many other types of cancers, anti-PD-1 therapy provides great promise. Melanoma is referred to as the case study for this new wave of cancer therapy, and researchers are now exploring immunotherapy across many cancer types. As MRA-funded researchers continue to study the mechanisms underlying therapy response and resistance, more and more patients will benefit from the knowledge gained.   Keep a look out for our next post discussing another protein integral to cancer’s ability to evade our immune systems – CTLA-4.