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Can Blood Be a Predictor of Therapeutic Response?

Aug 22, 2023, 16:27 PM by Nyla Sauter

Biospecimen Shared Resource recognized for its expertise with NCI U01 grant. 

The University of Cincinnati Cancer Center has received a National Cancer Institute U01 grant to investigate how to collect, process, and store peripheral blood mononuclear cells (PBMCs) in a way that maintains their cytotoxic activity to predict and monitor clinical response to immunotherapy. If this can be achieved, it would have profound implications on clinical trials and ultimately on patient care, its investigators say. 

“If we’re successful, then in the future, all we would have to do is to take a peripheral blood sample, send it for a cytotoxic assay, and you’d be able to determine earlier if we’re going to get a treatment response,” says Trisha Wise-Draper, MD, PhD, clinical/translational researcher and co-director of the Cancer Center’s Head & Neck Disease Center. 

The $1.1 million, five-year grant has several components that must be completed to reach that endpoint, says Kelsey Dillehay McKillip, PhD, director of the Cancer Center’s Biospecimen Shared Resource. The first step is identifying the optimal specimen collection, processing and storage conditions. “We’re assessing a variety of preanalytical variables to determine the best way to handle these cells to ensure that when we take them out of the freezer, they’re going to recapitulate the function of the cells at the time they were collected from the patient,” Dillehay McKillip says. 

The overall focus is to investigate a promising liquid biopsy approach that can be widely utilized based on immune profiling of PBMCs. Evidence suggests that such a liquid immune profile-based signature (LIPS) may, for example, predict both overall and progression-free survival in patients with metastatic cancer on immune checkpoint inhibitors (ICIs). However, use of LIPS is limited in widespread use due to the necessity of immediate processing and analysis, and the lack of availability of centers with sophisticated multicolor flow cytometers and/or expertise in analysis, Dillehay McKillip says. She adds that current PBMC processing limitations for biomarker analysis remain, and this proposal aims to directly confront these primary challenges. 

The team is currently in the first stages of the project, studying how various seemingly minute factors affect function, including various types of anticoagulants, collection tubes, collection to processing times, even the volume in which specimens are stored. “We’re trying to minimize the potential for preanalytical bias so that the goal of a reproducible ‘liquid biopsy’ that can be used to guide treatment and predict outcomes can be achieved,” Dillehay McKillip says.