Nobel Prize in Medicine Goes to Cancer Immunotherapy Pioneers

Megan Brooks

Two cancer researchers have been awarded the 2018 Nobel Prize in Physiology or Medicine for their discovery of how the immune system can be harnessed to attack tumor cells, which led to immune checkpoint inhibitor therapy.

Sharing the prestigious award are James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and Tasuku Honjo, MD, PhD, of Kyoto University in Japan.

The Nobel Assembly at Karolinska Institutet has today awarded the 2018 Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo.

"For more than 100 years scientists attempted to engage the immune system in the fight against cancer. Until the seminal discoveries by the two laureates, progress into clinical development was modest. Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed," the Nobel organization said in a statement.

The Birth of Cancer Immunotherapy

During the 1990s, in his laboratory at the University of California, Berkeley, Allison was one of several scientists who discovered that the protein CTLA-4 functions as a brake on T cells. Other research teams exploited the mechanism as a target to treat autoimmune disease. But Allison had other ideas.

Having developed an antibody that binds to CTLA-4 and blocks its function, he began investigating whether CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. Allison's team performed the first experiments at the end of 1994, and the results were "spectacular," the Nobel organization said. Mice with cancer were cured with an anti-CTLA-4 agent.

Promising clinical results soon followed from several groups, and in 2010, a key clinical trial showed striking effects in patients with advanced melanoma. "In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group," the Nobel organization said.

In 1992, Honjo discovered programmed cell death 1 (PD-1), another protein expressed on the surface of T cells. In a series of experiments, Honjo showed that PD-1 (like CTLA-4) also functions as a T-cell brake, but operates by a different mechanism.

In 2012, a pivotal study demonstrated clear efficacy in the treatment of patients with different types of cancer. "Results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable," the Nobel organization said.

The pioneering work of Allison and Honjo on immune checkpoint inhibitor therapy led to the development of several drugs, including ipilimumab (Yervoy, Bristol-Myers Squibb), the first of the checkpoint inhibitors, and the PD-1 inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co).

A large number of checkpoint therapy trials are currently underway against most types of cancer, and new checkpoint proteins are being tested as targets.

In 2013, cancer immunology was selected as the breakthrough of the year by the editors of Science, the flagship journal of the American Association for the Advancement of Science, as reported by Medscape Medical News.

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Comments

Dr. Lama AlSafadi|  Hematology
What about nutrition going natural do you think it can help ? I believe from experience lots of side effects and no solid cure with those very expensive medications

Dr. sudhakar kamat|  Pulmonary Medicine
I only want to talk on respiratory lung cancers.; surgery could be useful in a small minority-20%;rADIATION NEVER CURED ANYONE,CHEMOTHERAPY GAVE TEMPORARY IMPROVEMENT.in 25-30%Whatever i learned from literaturethere is benefit in another 10-20%.the stress to lung specialist,relatives and escalatory cost-?IS THIS ALL WORTH IN PRACTICE/MAY BE FOR NOBLE PRIZES

Dr. ALAN PODIS|  Urology
Although  recently retired from a career in Urology, I have a keen interest in Alzheimers disease, having lost my sister to this horrible fate.  At a  recent symposium on this subject one of the MD investigators described studies with mice and with controlled patient populations.  The studies utilized NIVOLUMAB and real results were noted ameliorating the terrible symptoms in the treated cohort.  The panel seemed quite excited to experiment further with this drug.

Dr. Richard Machange|  General Practice
They regard.

Dr. Susan HappellOpsomer
I’m going to have to agree with Dr. Crowder on this one. Others, including Dr. Gerson, and not affiliated with big pharma, preceded these gentlemen in establishing the basis for immunotherapy—for many disorders and diseases (not just cancer). The problem with this nobel prize winning therapy is, once again, harsh drugs with not enough side-effect-related research studies; subjecting those to whom the drugs are administered to hold false hope in both the cure and the unknown long term effects. While any advancement in cancer therapies is of course a plus, I’m concerned about any therapy that focuses on drugs (yet again) and not on the causes and lifestyle factors that, by changing, could ultimately stop cancer from starting.

 

Dr. Cheng Liu|  Pathology
Dr. Lieping Chen, the discoverer of PD-L1, was unfortunately and unfairly missed from the list.

Carolyn Crowder|  Psychologist
What about the work of Max Gerson in the 1940's.  He was blackballed by the monied interests of the burgeoning cancer treatment industry because he achieved amazing results with patients who had been sent home to die.  Immune therapy is nothing new!!!

Eleni Pellazgu|  Nurse Practitioner (NP)
@Carolyn Crowder i am all about nutrition( myself a whole food plant based for years), but as far as I am concerned no coffee enema can cure all cancers, plus there were no studies of Gerson, just anecdotal stories.

Pat Rios|  Other Healthcare Provider
There are hundreds of stories of people who have been cured by going on Gerson therapy, or becoming vegetarian, or doing just coffee enemas. Maybe do a little research so you can read some of them. Not everyone survives but about 80% do which is a higher number than any chemo or radiation therapy has ever achieved. I have met so many people who have told me they cured themselves of cancer after chemo almost killed them, or living a death sentence of viruses even MRSA,. Yet, once they switch to alternative therapy, after being told their chances of survival didn't look good, they survived to tell about it. I'm not knocking down medical research, having worked in it for year's, but alternative still holds a chance for survival. Whatever modality of therapy intuitively feels right, one should do it. As for lung cancer or lung issues, this is quite a different story, and where these brilliant men who won the Nobel Prize could help in more ways than one.

 

Suyash Gunjal|  Medical Student
Thank you!

 

Dr. Martha Twaddle|  Internal Medicine
The impact of these meds is not fully known. Yes, some of my patients who respond the best in terms of disease remission get significant side effects. Right now I have a gentleman who is likely going to die from a myasthenia gravis syndrome complication of his medication

 

Kevin Brooks|  Dentist/Oral Health Professional
These medications saved my life..30 months cancer free! Stage 4 melanoma. Thank you

 

Pamela J Morris|  Dentist/Oral Health Professional
Which drug were you given?

 

Charlene Morris|  Physician Assistant
This achievement is amazing and inspiring as well as tremendous effort at working towards combating cancer!

Dr. Olu Ogunsanwo|  Ob/Gyn & Women's Health
Attaboy to both scientists.

Massiha Ahmed|  Medical Student
That's a great a achievement. Congratulations to both winners.

But could the t cell brake while curing cancer trigger some other autoimmune disease in the body?

 

SETH ANDERSON|  Dentist/Oral Health Professional
You know, medical research is not nearly as celebrated as winning the SUPER BOWL, the WORLD SERIES, STANLEY CUP, or the NBA FINALS.  What these men have accomplished exceeds winning ALL OF THEM THE SAME YEAR!!!

 

Jan Matthews|  Other Healthcare Provider
Thank You!

 

Lely Netso|  Pharmacist
Hongera (congrats)

Dr. hemant sant|  Surgery, General
True when I diverted from being a Cancer GI Surgeon to A Preventive Oncology person I had to read my cell biology again to understand how check point inhibitors and IHC has impacted personal cancer therapy results .Kudos to all who erected such Edifice and still for benefit of gen next cancer Survivors .

Dr. James Ogilvie|  Orthopaedic Surgery
Incredible example of bench to bedside research. Congratulations. Now if a mechanism can be devised to deliver this therapy at an affordable price it will merit a Nobel prize in economics.

 

SOK-JA JANKET|  Other Healthcare Provider
@ROJA MALAR: the reference for this rationale is in JAMA.

Allison JP (2015). Immune Checkpoint Blockade in Cancer Therapy: The 2015 Lasker-DeBakey Clinical Medical Research Award. Jama 314: 1113-4.26348357

@Dr. Therry William: it works well 4 metastatic cancers. But only 33-50% responds to this therapy and the cost is high. I am going to lecture about "what are the predictors and mechanisms  to the responsiveness to this therapy" in November in Hamburg,  Germany at the "International Society of oncology and biomarkers" congress. Come and listen what I found out.

 

Mkojera Nicholaus|  Nursing Student
How can i listen while i am in Tanzania

 

Dr. kesha allen|  Emergency Medicine
I’m not a beneficiary of their specific work, but I am a beneficiary of immunotherapy and it’s advances for lung cancer survivors. This is wonderful for them and for all those their research has helped.

Dr. Zafar Khan|  Urology
what an achiement! changed the face of cancer treatment ! You are my heros. The whole mankind is indebted to you.

 

Dr. akshay shivchhand|  Internal Medicine
Nice job done.. Dr. Alice and Honjo.. sir William Coley will Definitely be happy with this work.

 

ROJA MALAR|  Medical Student
Give me detail mechanism behind it.

Dr. Therry William|  Internal Medicine
Quite Interesting!

How does this work in metastatic cancers??

 

Dr. Margaret Moore|  Neurology
@Dr. Therry William  yes

ABBIE Mansour|  Other Healthcare Provider
I would be interested how this has worked in metastatic prostate cancer. Any data on that?

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