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National Institutes of Health (NIH) Research Updates – March 2022

CATEGORY
NIH

DATE
March 7, 2022

The National Institutes of Health (NIH) is our nation’s medical research agency. Its mission focuses on scientific discoveries that improve health and save lives. Founded in 1870, the NIH conducts its own scientific research through its Intramural Research Program (IRP), which supports approximately 1,200 principal investigators and more than 4,000 postdoctoral fellows conducting basic, translational and clinical research. In this blog, we will highlight recent innovative NIH research.

Recent NIH Research

Scientists pinpoint mechanisms associated with severe COVID-19 blood clotting

A team of researchers, which includes those who work at the National Heart, Lung, and Blood Institute (NHLBI) have identified “rogue antibodies” that correlate with severe Covid-19 illness. The finding of this new study, may help shed light on the mechanisms leading to severe blood clotting associated with this disease.

Blood samples from 244 patients that were hospitalized for COVID-19 were analyzed and found to contain higher levels of the antibody IgG, which works in conjunction with other immune cells to fight off bacterial, viral and fungal infections. Elevated levels of IgG are also indicators of severe COVID-19 disease, such as in patients who required breathing assistance. While the role of IgG is to protect the body from pathogenic infection, in some cases, the response can become excessive and exacerbate illness.

The researchers also found that removing IgG from the COVID-19 blood samples led to a decrease in the molecular indicators of “blood vessel stickiness”. Conversely, when adding these same IgG antibodies to the control samples, the research team observed a blood vessel inflammatory response that can lead to clotting.

Circulating factors that lead to the “stickiness” of healthy blood vessels during COVID-19 infection may help explain why the virus can affect many organs, including the heart, lungs, and brain. The researchers note the potential benefits of screening patients with COVID-19 or other forms of critical illness for antiphospholipids and other autoantibodies, at earlier points of infection, may help identify patients at risk for extreme blood clotting, vascular inflammation, and respiratory failure and could inform treatments to protect blood vessels or fine-tune the immune system of these patients.

Gene expression profile could enable rapid identification of anti-tumor immune cells for personalized immunotherapy

IRP scientists have discovered unique expression profiles in 50 genes that aid in identifying tumor-infiltrating lymphocytes (TIL) targeting metastatic solid epithelial tumors. The recent study was led by Dr. Steven Rosenberg, chief of the Surgery Branch at the Center for Cancer Research, National Cancer Institute (NCI), who pioneered the development of cell-based immunotherapy, a highly personalized form of cancer treatment that uses a person’s own immune system to fight tumor cells. His work led to the adoptive transfer of genetically modified immune cells which has resulted in tumor regression in patients with metastatic cancer.

In prior studies, Rosenberg’s team needed to look at every potential mutation in a tumor that could be a target. Years of research led to the development of a highly sensitive assay capable of identifying the gene expression profiles of a few rare lymphocytes that recognize mutated cell surface proteins of cancerous cell and is agnostic to the type of tumor a patient has. The identification of these lymphocytes could help advance the development and effectiveness of personalized cancer immunotherapies for patients whose cancers do not respond to standard treatments.

NIH study advances personalized immunotherapy for metastatic breast cancer

A new study led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research showed promising results in using an individual’s own tumor-fighting immune cells (TILs) to treat people with metastatic breast cancer.

Immunotherapy is a treatment that helps a person’s own immune system fight cancer. However, most available immunotherapies, such as immune checkpoint inhibitors, have shown limited effectiveness against hormone receptor–positive breast cancers, which are the majority of breast cancers. The immunotherapy approach using TILs, T cells that are found around the tumor, was pioneered in the late 1980s by Dr. Steven Rosenberg and his colleagues at NCI. TILs can target tumor cells that have specific proteins on their surface, called neoantigens that are produced when mutations occur in the tumor DNA, that the immune cells recognize.

In an ongoing clinical trial of 42 women with metastatic breast cancer, 28 were able to generate an immune reaction against their cancer. This new approach was used to treat six women using reactive TILs that were grown to large numbers in the lab. The researchers then returned the immune cells to each patient via intravenous infusion. Each patient was given four doses of the immune checkpoint inhibitor pembrolizumab (Keytruda) before the infusion to prevent the newly introduced T cells from becoming inactivated.

Following treatment, tumors shrank in three of the six women. One who was part of the original 2018 study remains cancer free to this day. The other two women experienced tumor shrinkage of 52% and 69% after 6 months and 10 months, respectively. However, some disease returned and was surgically removed. Now, those women now have no evidence of cancer approximately five years and 3.5 years, respectively, after their TIL treatment.

“We’re using a patient’s own lymphocytes as a drug to treat the cancer by targeting the unique mutations in that cancer,” says Dr. Rosenberg. “This is a highly personalized treatment.” He noted that this new immunotherapy approach could potentially be used for treating people with other types of cancer as well.

Scientists identify new features of a rare lung disease

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that mostly affects women of reproductive age. This progressive condition is caused by the abnormal growth of cells in the lungs, kidneys, lymph nodes and other organs and tissues. Diagnosis can be difficult due to the rare nature of the disease and current therapies target symptom management and slowing the progression of the disease.

In a recent study, a team of researchers, including scientists from the National Institute of Health (NIH), have identified a “mixed phenotype,” or differences in physical expression in the lymphatic endothelial cells. These cells appeared to resemble cells in lymphatics as well as blood endothelial cells. The characteristics were also noted in a small percentage of lung cells provided by people living with idiopathic pulmonary fibrosis (IPF), another rare lung disease, but were not observed in cells from Kaposi’s sarcoma patients or healthy individuals.

The accumulation of LAM cells within the lungs form cysts that can impede airflow, making it hard to breathe. LAM cells in the lung reside in nodules, which are small clusters of LAM and other cells that line the cysts and may be disseminated. These lung nodules also contain lymphatics, part of the lymphatic system, which supports circulation and immune function. Lymphatic endothelial cells line the nodules and provided new insight about LAM. Researchers are hopeful that ongoing research and future studies will lead to personalized therapies for people living with LAM and other rare lung conditions.