Research Roundup: Disarming Overactive Neutrophils in the Lungs and More
This week, researchers presented results from studies on treatments in lung disease, Alzheimer’s and various cancers. Here's a look at that and more.
ASTRUM-005: The first successful mAB Phase III trial for SCLC treatment
The ASTRUM-005 trial with serplulimab became the first successful Phase III clinical trial study for small cell lung cancer, (SCLC).
Serplulimab is an anti-PD-1 monoclonal antibody (mAb), or a drug that targets the PD-1 checkpoint, increasing the body’s natural immune response against cancerous cells.
When used in conjunction with chemotherapy as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), the treatment was found to be effective.
Other researchers have attempted to make an anti-PD-1 mAb, but this is the first successful clinical study. The study also showed safety and consistent efficacy over time.
In being accepted by the Journal of the American Medical Association (JAMA), the study gives the researchers hope that serplulimab will become the world’s first anti-PD-1 mAb treatment and the first-line treatment for SCLC in the next five years.
Disarming Neutrophils and Treating ARDS
Nicholas Tonks, a professor of cancer research at Cold Spring Harbor Laboratory (CSHL), and his team discovered a new drug that counteracts the response of overactive neutrophils in the lungs.
The drug works by inhibiting protein PTP1B, which impacts the aging process of neutrophils, and when inhibited, speeds up that aging process. In aging the cells more rapidly, they lose their potency, making it so that regardless of the number of cells that accumulate in the lungs, no serious damage will be done.
Neutrophils are the most abundant type of white blood cell, and they are the first line of defense against foreign invaders and infection. These cells are extremely helpful in defending the body, but when they are overactive, they can damage the body’s own tissue.
Because the lungs have so many blood vessels, they are particularly susceptible to attack from over-active neutrophils. When the attacks are severe, they can lead to acute respiratory distress syndrome (ARDS), which is the leading cause of death due to COVID-19.
One of Tonk’s students investigated if using a PTP1B drug could lessen the consequences of the overactive neutrophils in mice models and found that all of the treated mice survived, compared to less than half of untreated mice. Tonks and his team are working with DepYmed, Inc. to take the PTP1B inhibitor drug candidates to clinical trials.
Circulatory Approach Could Slow Progression of Alzheimer's
A study conducted by Inés Moreno, a researcher at the University of Malaga in collaboration with the University of Texas, has identified a new, non-invasive therapy that could slow the progression of Alzheimer’s disease (AD).
In her paper, Moreno showed she was able to significantly reduce the amyloid plaques in mice with AD by exchanging the blood in the veins of the sick mice with the blood of mice without AD. Not only did this procedure work to improve amyloid-beta build-up in the brain, but there was an improvement in spatial memory test performance, suggesting memory improvement.
In AD, the standout neurological change is the presence of excess proteins in the form of plaque. This plaque, called amyloid-beta, is unique to AD, and previous research suggests that it is the overgrowth and deposition of this substance that is central to the disease.
While the exact mechanism behind this improvement is unknown, data suggest there may be movement of amyloid-beta from the brain into the bloodstream, essentially washing out the buildup.
Further research needs to be done, but these results provide a new target for novel AD therapies and suggest there may be an answer soon in the future.
Clinical Study Finds Active Target for Treatment of Multiple Myeloma
In previous studies using similar CAR-T cell therapies, researchers had success in primary treatment, but relapse was common. In this study, 17 patients were treated with varying levels of the therapeutic. The researchers found that patients who had previously relapsed after similar treatments had the same responses to this new treatment as those who had not received CAR-T cell therapy before.
The results confirmed that their target, GPRC5D, is an active immunotherapeutic target in multiple myeloma.
The researchers “look forward to advancing this program either as a stand-alone therapy or as a combination therapy with BCMA-targeting CARs,” stated Eric Smith, M.D., Ph.D., one of the lead researchers on the team.