Grants - Translational Grants - Georgia - 2021

Chrystal Paulos, PhD & Ragini Kudchadkar, MD

Though survival for patients with advanced melanoma has improved over the last decade with the introduction of anti-PD-1 antibodies, half of patients treated with this therapy have disease that recurs. Both combination immunotherapies and single-agent anti-PD-1 antibodies are currently used to treat melanoma. However, combination therapies have higher responses but also higher toxicity rates. Currently, there are no definitive biomarkers that can predict which therapy choice is correct for metastatic melanoma patients.  

This project is focused on understanding why patients are resistant to PD1-based therapies.  We recently discovered that patients with more CD26 (a type of protein) found in the tumor’s immune cells are more responsive to treatment. These collective findings beg the question: What is the role of CD26 in the immune response to melanoma?  

To answer this question we will study CD26 melanoma immunity using melanoma patients’ blood and tumor samples.  This data will allow CD26 to be used as a biomarker in prognosis for patients treated with PD-1-based therapies, and allow for future studies for clinicians to use CD26 as a predictive biomarker to help select the appropriate treatment for a patient, i.e., combination or single-agent immunotherapy. 

The role of CD26 activity in melanoma immune response will be defined by this project. Findings from this research will be the basis for future clinical trials to target CD26 in order to enhance immunity against tumors that are unresponsive to PD-1-based therapy in order to create new hope for patients with PD-1-refractory melanoma.