NIH grant funds cancer vaccine research

NIH grant funds cancer vaccine research

image: Partially solid lung cancer lesions showing a region with proliferation along the surface of intact alveolar walls without invasion (yellow arrow) and developing an invasive component (blue arrow). The normal lung region is indicated (green arrow).
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Credit: Mitchell Martin and Dr. Vivek Mittal

A multidisciplinary team of researchers from Weill Cornell Medicine has received a five-year, $5.7 million grant from the National Cancer Institute of the National Institutes of Health to fund a center to develop messenger RNA (mRNA) vaccines to prevent cancer. development of cancer in risk groups.

The Weill Cornell Medicine CAP-IT Center for LNP RNA Immunoprevention has been selected as one of two founding members of the Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT), an NCI-funded collaborative research network to discover agents that prevent or intercept cancer in high-risk populations.

“Prevention truly is the best cure for cancer,” said lead researcher and project leader Dr. Steven M. Lipkin, Gladys and Roland Harriman Professor of Medicine and Vice Chairman of Research at the Sanford Department of Medicine and Joan Weill of Weill Cornell Medicine. .

Dr Lipkin and his colleagues are working on vaccines containing mRNA – a molecule that instructs cells to produce specific proteins – with the aim of activating the immune system to recognize and destroy cancer cells carrying these proteins at an early stage. This strategy could deter malignant cell populations from accumulating enough mutations to evade the body’s immune response. The approach also aims to prevent the creation of a tumor microenvironment, made up of molecules, cells and blood vessels that fuel cancer and suppress the immune system.

The vaccines will use the same type of mRNA technology as the Moderna and Pfizer COVID-19 vaccines, which were based on at least a decade of prior scientific cancer investigation.

Because the mRNA cargo must be protected from degradation, it will be encapsulated in a fatty envelope composed of lipid nanoparticles, which are made in the laboratory of Dr. Shaoyi Jiang, Professor Robert S. Langer ’70 Family and Friends at the Meinig School of biomedical engineering at Cornell’s Ithaca campus.

Studies of mRNA vaccines will begin in mice, with the goal of conducting clinical trials within the next five years. The researchers plan to conduct several research projects.

The first is to develop and validate an mRNA vaccine against Lynch syndrome, an inherited genetic disease that significantly increases the risk of developing colon cancer and other cancers before the age of 50. The research team plans to design these vaccines so that they activate the immune system’s T cells to prevent cancer. “T cells recognize malignant cells, attach to them, and kill them,” said Dr. Lipkin, who is also program manager for cancer genetics and epigenetics at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

The second project is to develop and evaluate an mRNA vaccine for precancerous lung lesions, known as non-solid lung nodule (NSN) precancerous neoplasms.

“There is currently no effective way to manage these lesions so that they do not turn into cancer, other than to remove them surgically,” said lead researcher Dr. Nasser Altorki, chief of thoracic surgery at Weill. Cornell Medicine and NewYork-Presbyterian/Weill Cornell. Medical Center.

Researchers hope to one day develop an mRNA vaccine that targets shared groups of antigens — or foreign or abnormal particles that generate an immune response — in people with lung cancer. Another option is to develop personalized vaccines directed against alterations in the genetic structure of each patient’s tumor, said Dr. Altorki, who is also vice president of cardiothoracic surgery, the David B. Skinner, MD, professor of thoracic surgery, and head of the experimental therapeutics program at the Meyer Cancer Center.

“Now is the time to develop these lung cancer vaccines,” said lead researcher Dr. Timothy McGraw, professor of biochemistry in cardiothoracic surgery and biochemistry and head of the cancer biology program at Weill Cornell Medicine. “We know a lot about the immunological changes that allow lung tumors to grow, as well as some of the associated mutations.”

Preclinical models of precancerous lung cancer are essential to assess the therapeutic efficacy of vaccines against cancer-specific proteins identified in patients. Since such a model was not available, the Mittal lab recently developed and characterized an oncogene-driven model of lung cancer that resembles human precancerous disease.

“We were pleasantly surprised to observe very similar cellular and molecular changes in mice and humans,” said lead researcher Dr. Vivek Mittal, Gerald J. Ford – O. Wayne Isom Professor of Cardiothoracic Surgery and Director from the Neuberger Berman Lung Cancer Laboratory. .

With additional funding outside of this grant, researchers are pursuing other mRNA vaccination projects, including targeting a pediatric cancer syndrome called Constitutional Error Repair Deficit (CMMRD) and infection with Nucleated Fusobacteria a bacterium that promotes the development of colon cancer.

“We envision this program as a platform for the creation of several types of cancer vaccines,” said Dr. Lipkin. “We have the technology to make vaccines that carry different mRNA cargoes to activate the immune system in various ways to prevent cancer.”


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