NOBEL PRIZE FOR MEDICINE-2018
REVOLUTIONIZING CANCER TREATMENT
The press announcement on 1st October 2018 by The Nobel Assembly at Karolinska Institute came as a new ray of hope in the field of cancer treatment when the Nobel Prize for Medicine-2018 was jointly awarded to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.
The discovery by these two will significantly help many cancer patients all across the globe. Therefore it becomes mandatory to understand the concept of this negative immune therapy.
The immune system usually has the capability of recognizing “self” cells from “non-self” cells. It will attack the foreign particles or cells in our body and create an immunological response. But immune system can become hyperactive if not stopped at a particular time. This hyperactivity of immune cells can lead to excessive proliferation and growth of cells leading to tumours and finally Cancer.
Now what Allison and Honjo did was discover certain proteins in the body which can act as brakes to the immune system. These brakes when inhibited the immune system, led to the unleashing of certain cells in the body called T-cells which attacked the cancer cells. Allison and Honjo worked in different labs and discovered different proteins with different mechanisms of working which resulted in the same attack on cancer cells. The proteins discovered were CTLA4 & PD1.
These two function as immunological check-points and their activation can trigger mechanisms to inhibit various types of cancer including lung cancer, renal cancer, lymphoma and melanoma. Initially tested upon mice in labs, these two checkpoints have shown positive results and now have been tested in humans pharmacologically but to a limited extent.
The discovery in this zone of checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed. Further implementations to such therapy mechanisms can prove as a boon to all the cancer patients worldwide. Checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have yielded durable responses in a significant percentage of cancer patients in recent years, leading to U.S. FDA approval of six checkpoint inhibitors for numerous cancer indications since 2011for melanoma. In the next few years it is expected that the approval will be for other cancer types like lung cancer, kidney cancer, bladder cancer, prostate cancer, lymphoma, and many other tumour types. As the clinical response is durable only in few patients, studies on biomarkers are going to identify patients in clinical diagnosis who can undergo this treatment.
Certain drugs have entered the clinics after being approved across. Ipilimumab, a fully human antibody to human CTLA-4, entered clinical trials in the late 1990s and early 2000s. Importantly, durable responses were observed in about 20% of patients living for more than 4 years, including a recent analysis indicating survival of 10 years or more for a subset of patients. Nivolumab received FDA approval in December 2014 as a treatment for patients with metastatic melanoma. In addition, nivolumab was FDA-approved in March 2015 for patients with previously treated advanced or metastatic non–small cell lung cancer based on a phase III clinical trial, which reported an improvement in overall survival for patients treated with nivolumab as compared to patients treated with docetaxel chemotherapy. Ongoing clinical trials for the same drugs on other variants of cancer other than melanoma are showing positive results and in the near future these drugs can revolutionize cancer treatment.
YODDHAS aims at creating awareness about this new step in science and hopes to reach out to all patients and caregivers across.
• The future of immune checkpoint therapy (Review article- J.Allison and P.Sharma)