MUSC Hollings Cancer Center is working with partner institutions to overcome barriers to lung cancer screening among Black communities in South Carolina and across the southeastern United States.Credit: da-kuk/ Getty images
John Wrangle got his start in cancer research by working summers at a lab during high school, and he never looked back. “Cancer research is the only profession I have ever wanted,” says Wrangle, a researcher and oncologist at MUSC Hollings Cancer Center in Charleston, South Carolina. Today, Wrangle develops novel immunotherapies for lung cancer, and along with Hollings colleagues, he works to expand state-wide access to screening and treatments for the disease.
Lung cancer is the world’s leading cancer killer, but not everyone is at equal risk. Black Americans, for instance, are diagnosed later and die from lung cancer at rates higher than their white counterparts. The disparities are stark in South Carolina, where two thirds of the population live in rural and medically underserved areas, according to Gerard Silvestri, a researcher and lung cancer pulmonologist at Hollings, the state’s only National Cancer Institute-designated cancer centre. Tobacco use is the top risk factor for lung cancer, and smoking prevalence is highest among people living below the federal poverty level, “who are difficult to reach”, says Silvestri. “Many of the people I see come from more than 50 miles away, and some can’t afford the gas to get here.”
Hollings, which is part of the Medical University of South Carolina (MUSC), is tackling the state’s lung cancer disparities from two angles. One key objective is to make clinical trials and cutting-edge therapies available to the state’s population. “We want to ensure we have the infrastructure and fundamentals to bring science directly from the lab to our patients,” Wrangle says. His team has completed a phase Ib/II trial of a promising investigational treatment designed to extend the efficacy of immune checkpoint inhibitors and deliver enhanced clinical benefit to those who do not initially respond to treatment.
The other priority is to boost access to screening with low-dose computed tomography scans of the chest1. The effort at Hollings targets people aged between 50 and 80 with a 20+ year history of smoking at least one pack of cigarettes on average per day. The goal is to save lives by diagnosing lung cancer during early stages, when five-year survival rates after treatment range up to 92%2.
Gerard Silvestri and Marvella Ford are working on lung cancer biomarker research and increasing screening rates among Black communities.Credit: Medical University of South Carolina
Screening for underserved communities
Newly awarded grants are facilitating these efforts. In March 2022, Hollings won a US$3 million, four-year Stand Up To Cancer grant from Bristol Myers Squibb. The grant makes Hollings part of the Southeastern Consortium for Lung Cancer Health Equity (SC3), a group that also includes the Massey Cancer Center at Virginia Commonwealth University and the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.
Together these institutions are testing a new approach to overcome barriers to lung cancer screening among Black communities, which include economic and logistic hurdles as well as fear and mistrust. The principal investigator of the Stand Up To Cancer grant at MUSC is Marvella Ford, a behavioural scientist who leads community outreach and engagement efforts at Hollings.
According to Ford, the approach relies on community health workers, who will identify patients at federally qualified health centres (FQHCs) in each state. From there, social work ‘navigators’ will guide the patients to lung cancer screening services offered at participating SC3 cancer centres. The navigators will identify resources to help overcome potential barriers to screening. The FQHCs provide access to primary and preventive care regardless of a person’s ability to pay. A primary outcome under the grant, Ford says, is to “assess the change in percent increase in lung cancer screening rates at each of the SC3 sites”.
Silvestri will lead the grant’s basic science component, creating a biorepository of saliva and blood samples provided by Black people eligible for lung cancer screening. The aim is to identify biomarkers for classifying lung cancer risk. “We’re doing that in the context of reaching rural and underserved areas,” Silvestri says. “Black people develop lung cancer at earlier ages and with less smoking history than white counterparts. Defining the relationship between their living circumstances and lung cancer biology is incredibly important.”
Meanwhile, a US$1.2 million grant awarded to Ford and Silvestri by the Duke Endowment in September 2022 is allowing Hollings to further expand biomarker research and cancer screening at its regional hospitals. These hospitals — as well as a new MUSC Health facility scheduled to open in Williamsburg County in 2023 — serve largely Black and rural people who, Ford says, tend to view lung cancer as a death sentence. Hollings researchers want to change that perception by showing that with early detection and treatment, people can often live — and thrive — for years after a lung cancer diagnosis.
John Wrangle, researcher and oncologist at MUSC Hollings Cancer Center.Credit: Medical University of South Carolina
Prolonging the potency of immunotherapy
Along those lines, drugs that turn the body’s immune defences against tumours have been a game-changer in lung cancer. “With immunotherapy,” Wrangle notes, “we went from a median overall survival of about six months with metastatic lung cancer to being able to talk about 20% of our patients achieving an overall survival of four years.”
Resistance to immunotherapy typically sets in over time. But working with racially diverse cohorts of patients, Wrangle’s team has developed an investigational treatment that is designed to extend the potency of pembrolizumab, an approved immunotherapy. Known as N-803, the treatment combines pembrolizumab — which targets PD-1 surface receptors on T cells — with an IL-15 cytokine engineered for sustained anti-tumour activity.
The two drugs work in complementary ways: pembrolizumab inhibits PD-1, a molecular checkpoint that blunts T cell reactions against cancer, while engineered IL-15 stimulates tumour-killing CD8+ and natural killer T cells. Importantly, IL-15 puts those cells into action without simultaneously activating CD4 T cells, and that broadens N-803’s therapeutic index. Doctors could potentially give doses high enough to augment and restore pembrolizumab’s anti-cancer activity, but without pushing the immune system into overdrive.
N-803 has cleared phase Ib/II clinical trials3, specifically in patients with metastatic, non-small cell lung cancer (NSCLC) who no longer respond to pembrolizumab alone. Based on preliminary signs of efficacy in these studies — the phase II section of the trial has been completed but results have not yet been published — the drug has now moved into the NCI and Southwest Oncology Group’s Lung-MAP phase III clinical trial, which is testing many targeted therapies for NSCLC simultaneously.
“N-803 has generated a huge amount of enthusiasm,” says Wrangle. And key to the rigour behind its ongoing development is Hollings’ place at the heart of a diverse population in South Carolina. “Too many trials suffer from racial homogeneity and that raises concerns about how much the results can be generalized,” Wrangle says. “We are grateful we have a diverse community to serve.”