The University of Texas Health Science Center at Houston (UTHealth) scientists working to increase the effectiveness of cancer drugs and the number of adolescents taking the human papillomavirus (HPV) vaccine have been awarded grants totaling $1.2 million from the Cancer Prevention & Research Institute of Texas (CPRIT).
To date, UTHealth has received 58 CPRIT grants for a combined $84 million.
Eva Sevick, PhD, received a $900,000 research grant to improve the efficacy of immunotherapy drugs. Ross Shegog, PhD, MPH, and Lara Savas, PhD, were awarded a $300,000 prevention grant to expand the use of proven strategies to improve immunization rates.
Sevick’s research is focused on the delivery of drugs through the body’s second vascular system – the lymphatic system.
The lymphatic system is a unidirectional vasculature that delivers immune cells and antigens through lymph nodes where T cells are educated to attack harmful antigens, said Sevick, director of the Center for Molecular Imaging at McGovern Medical School at UTHealth. Once T cells are activated, they leave lymph nodes and lymphatic vasculature, which empties into the bloodstream to mount an immune response throughout the body.
“Most cancers hijack the immune system by preventing the successful education of T cells in tumor-draining lymph nodes. Checkpoint blockade immunotherapies seek to reverse cancers’ immune escape by blocking signaling in the tumor-draining lymph nodes that inhibit anti-tumor immunity,” she said.
Sevick said these therapies are given intravenously with inefficient delivery to lymph nodes, particularly tumor-draining lymph nodes. Because large intravenous doses are needed to reach lymph nodes, the immune system is often indiscriminately overstimulated, causing immune-related adverse events that limit their efficacy.
In preclinical models, Sevick’s team has administered these drugs directly into the lymphatics to maximize drug exposure to tumor-draining lymph nodes and improve anti-tumor immunity. According to Sevick, when translated into humans, lymphatic delivery should maximize exposure to tumor-draining lymph nodes while reducing exposure to the entire immune system, hopefully avoiding immune-related adverse events.
With their CPRIT grant, Sevick’s team will further develop lymphatic infusion of checkpoint blockade immunotherapies in a preclinical model of melanoma before demonstrating lymphatic delivery approaches in melanoma patients.
Sevick is the Nancy and Rich Kinder Distinguished Chair in Cardiovascular Disease Research at UTHealth and a member of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.
With appointments at UTHealth School of Public Health, Shegog and Savas are developing and testing a web-based program to help primary care clinics in Texas improve their vaccination rates for HPV.
According to the Centers for Disease Control and Prevention, an estimated 79 million Americans are currently infected and almost all males and females will be infected with at least one type of HPV at some point in their lives. Importantly, approximately 19,200 cancers in women and 11,600 cancers in men are caused each year by HPV infection.
“This project follows a successful collaboration by UTHealth, Baylor College of Medicine, and Texas Children’s Pediatrics in which HPV vaccination rates increased from 54 percent to 77 percent,” Shegog said.
Called the Adolescent Vaccination Program Implementation Tool, it works by encouraging the use of proven vaccination strategies such as clinics having a designated vaccination champion, making doctors aware of the number of eligible patients they vaccinate and goals to increase their numbers, training doctors with skills to dispel vaccine hesitancy in their patients, creating electronic immunization reminders for caregivers, and promoting a smartphone application called HPVCancerFree.
“A robust evidence base exists for strategies to increase HPV vaccination,” said Shegog, who is also on the faculty of UTHealth School of Biomedical Informatics. “Despite this, adoption of these strategies in clinics has been piecemeal. Lacking is a readily adoptable multilevel approach that allows clinics to adopt multiple HPV vaccination strategies.”
CPRIT has awarded grants totaling more than $2.26 billion. CPRIT has passed the two-thirds mark in the state’s historical 2007 constitutional commitment of $3 billion to fight cancer.