Novel Biomarker Predicting Response to Checkpoint Inhibitor Therapy in Metastatic Melanoma

Technology

This invention consists of a new baseline biomarker to predict the outcome of immune checkpoint blockades (ICBs), mainly PD-1 inhibitors, in metastatic melanoma patients. The researchers investigated the expression signatures of baseline peripheral CD8+ T-cells, which are known to play a role in anti-PD-1 anti-tumor immunity. When examining the protein expression signatures of these CD8+ T-cells in a cohort of 120 metastatic melanoma patients, a novel protein that is strongly associated with anti-PD-1 resistance was identified. The protein discovered is largely unknown in terms of its function. It is expressed almost fourfold in patients resistant to anti-PD-1 immunotherapy compared to responding patients. Importantly, these results were replicated when the study was repeated on a different patient group.

Background

Melanoma is the deadliest type of skin cancer and its incidence has been rising over the last 30 years in the US, mostly due to aging populations. Metastatic melanoma is extremely deadly, with a five-year survival rate of less than 15%. One of the most promising therapies for metastatic melanoma patients are immune checkpoint ICB drugs. ICBs (e.g., nivolumab and pembrolizumab) are highly beneficial in treating these patients, increasing their life expectancy and quality of life overall. However, not all patients respond to these drugs and many develop side effects. Currently, there is no effective way to predict the efficacy of ICB therapies and whether they would be beneficial to specific individuals. NYU scientist Tomas Kirchhoff found a novel biomarker that can predict if patients will respond to these widely-used immunotherapies. 

Applications

• Predicting the response of metastatic melanoma patients to new, efficient immunotherapies Despite these drugs’ efficacy, many patients do not respond, and therefore would benefit from avoiding the adverse effects of these drugs. 
  
• Better understanding the scientific pathways involved in ICB resistance This class of immunotherapies is becoming very common in many cancer types and increasing its efficacy by inhibiting this protein target or other targets in its pathway could be highly lucrative to pharmaceutical companies.
  

Advantages

• A promising step towards prognostication of the likelihood of success when metastatic melanoma patients are given certain ICB drugs. This allows for a personalized medicine approach in which only patients who are likely to respond to the immunotherapy will be administered the drug.
  
• A baseline biomarker of host immune response, likely independent of the tumor microenvironment.
  

IP Status

Provisional patent application pending