Predicting Response

How Liquid Biopsy – and an Important Partnership – is Opening New Doors in IO 

What if we could tell how a patient would respond to a treatment before they even started on a medicine?

What once seemed impossible may no longer be so: Mounting evidence in the field of immuno-oncology ­ and in particular research pioneered by scientists at MedImmune, the global biologics research and development arm of AstraZeneca suggests that the tumor mutational burden (TMB) biomarker could be a reliable predictor of patient response, especially in the PD-1/PD-L1 and CTLA4 blockade. ­­

So why is TMB an important biomarker for IO treatments?

TMB is represented as the number of mutations per megabase across a sufficiently large section of a tumor’s genome, and researchers have found that greater mutational burden is often associated with a greater number of neoantigens present within a tumor. This is significant, because patients with a high TMB could also have an associated increase in T cells, which are able to recognize neoantigens expressed by tumor cells and kill them. 

Unfortunately, accessing TMB data from tumor biopsy can be a challenge. Not all patients have sufficient tissue or are able to safely undergo the biopsy procedure. These challenges limit the use of tumor biopsy based TMB analysis.

But what if new methods could provide more consistent and convenient access to TMB data? 

This critical question is what led Dr. Koustubh Ranade, Vice President of Translational Medicine at MedImmune, and our partners at Guardant Health to spend the past two years pioneering a new method for blood-based TMB (bTMB) analysis, a minimally invasive blood-based test, that could be key to advancing patient response to immunotherapy moving forward.

The technology leverages circulating tumor DNA (ctDNA), tumor-derived DNA that is shed into a patient’s blood stream, to access a tumors genomic sequencing data while being minimally-invasive for patients.

According to Dr. Ranade, “The ability to remove barriers to traditional biopsy through bTMB analysis will hopefully allow more patients to be guided to the appropriate immunotherapy treatment.”

By better understanding the biology of various types of tumors, MedImmune researchers hope to continue to identify new ways to attack tumors with both high and low mutation burden, with the goal of providing patients with treatment options that are tailored to the biology of their specific tumor cells, and therefore, more likely to be efficacious