Medicine-carriers made from human cells can cure lung infections

SPOKANE, Wash. – Scientists used human white blood cell membranes to carry two drugs, an antibiotic and an anti-inflammatory, directly to infected lungs in mice.

The nano-sized drug delivery method developed at Washington State University successfully treated both the bacterial growth and inflammation in the mice’s lungs. The study, recently published in Communications Biology, shows a potential new strategy for treating infectious diseases, including COVID-19.

“If a doctor simply gives two drugs to a patient, they don’t go directly to the lungs. They circulate in the whole body, so potentially there’s a lot of toxicity,” said Zhenjia Wang, the study’s corresponding author and an associate professor in WSU’s College of Pharmacy and Pharmaceutical Sciences. “Instead, we can load the two types of drugs into these vesicles that specifically target the lung inflammation.”

Wang and his research team have developed a method to essentially peel the membrane from neutrophils, the most common type of white blood cells that lead the body’s immune system response. Once emptied, these membranes can be used as nanovesicles, tiny empty sacks only 100 to 200 nanometers wide, which scientists can then fill with medicine.

These nanovesicles retain some of the properties of the original white blood cells, so when they are injected into a patient, they travel directly to the inflamed area just as the cells would normally, but these nanovesicles carry the medicines that the scientists implanted to attack the infection.

In this study, first author Jin Gao, a WSU research associate, loaded the nanovesicles with an antibiotic and resolvinD1, an anti-inflammatory derived from Omega 3 fatty acids, to treat lungs infected by P. aeruginosa, a common potentially fatal pathogen patients can catch in hospital settings. The researchers used two drugs because lung infections often create two problems, the infection itself and inflammation created by a strong immune system response.

Toxicity studies and clinical trials would have to be conducted before this method could be used in human patients, but this study provides evidence that the innovation works for lung inflammation. If the method is ultimately proven safe and effective for humans, Wang said the nanovesicles could be loaded with any type of drug to treat a range of infectious diseases, including COVID-19.

“I think it’s possible to translate this technology to help treat COVID-19,” said Wang. “COVID-19 is a virus, not a bacterial pathogen, but it also causes an inflammation response in the lung, so we could load an antiviral drug like remdesivir into the nanovesicle, and it would target that inflammation.”

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Trial targets deadly lung cancer

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IMAGE: Associate Professor Sonja Klebe, leader of Asbestos Associated Disease research at Flinders University
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Credit: Flinders University

With more than 650 Australians diagnosed with malignant mesothelioma last year, Flinders University is leading new research to discover alternatives to chemotherapy and even prevent deaths by early detection in future.

One novel approach, using natural therapeutic benefits of curcumin, a key component of the spice turmeric, will be put to the test in a clinical trial in 2021 as part of world-leading research at Flinders University.

While asbestos is now banned from being used for new buildings, many houses still contain asbestos, so exposure during renovations is common. Australia has one of the highest per-capita rates of asbestos-related disease in the world.

Flinders University researchers are studying the safety and feasibility of using a form of intrapleural liposomal curcumins to benefit patient survival and quality of life – with fewer toxic side-effects than chemotherapy.

“That’s why it’s important to explore alternative therapies and facilitate early diagnosis to reduce suffering and support early intervention measures,” says Flinders University lead researcher Associate Professor Sonja Klebe.

As well, the researchers are looking for early diagnostic methods with a special lung fluid test. “In most cases, malignant mesothelioma is not diagnosed until it is in the late stages,” she says. “We’re hoping to find a way to test for the disease before it becomes invasive.”

Patients diagnosed with malignant mesothelioma, the cancer caused by asbestos exposure, experience poor survival of 6-12 months following diagnosis and a five-year survival of less than 5%. Therapeutic options are limited due to high resistance rates to chemotherapy and the advanced age of patients (median age 75).

Associate Professor Klebe’s team will test the safety and feasibility of intrapleural liposomal curcumin to benefit patient survival and quality of life. Future treatments are expected to have fewer toxic side-effects than chemotherapy.

In addition, the researchers are investigating methods to facilitate early diagnosis, using novel techniques on the lung fluid that is drained in the early stages of diagnosis.

“In most cases, malignant mesothelioma is not diagnosed until it is in the late stages,” she says. “We’re hoping to find a way to test for the disease before it becomes invasive.”

In time for Asbestos Awareness Month in November, the experts warn the high number of cases could persist for years with hundreds more cases of the deadly disease possible after latency of more than 30 years from work-related (builders, plumbers, gasfitters, mechanics and marine engineers) or other exposure. Firefighters may also be at risk after the devastating bushfires razed old buildings and sheds across Australia.

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See the latest research publications:
‘Malignant mesothelioma in situ: diagnostic and clinical considerations’ (2020) by E Pulford, DW Henderson and S Klebe published in Anatomical Pathology (Vol 52, Iss 6, page 635-642)
DOI: 10.1016/j.pathol.2020.06.010

See also:
The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas (2020) by S Prabhakaran, A Hocking, C Kim, M Hussey and S Klebe has

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Genprex Unveils New Branding for Upcoming Combination Clinical Trials in Non-Small Cell Lung Cancer

New branding will support upcoming combination clinical trials, including the Company’s trial combining REQORSA™ immunogene therapy drug with AstraZeneca’s Tagrisso®, which received FDA Fast Track Designation earlier in 2020

Genprex, Inc. (“Genprex” or the “Company”) (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, today announced the launch of new branding for its upcoming oncology clinical trials combining its lead drug candidate, REQORSA(quaratusugene ozeplasmid), with AstraZeneca’s Tagrisso® (osimertinib), which received U.S. Food and Drug Administration (FDA) Fast Track Designation earlier this year, and for the combination of REQORSA with Merck’s Keytruda® (pembrolizumab), for the treatment of non-small cell lung cancer (NSCLC).

These trials will use the trial brand “Acclaim,” which the Company believes evokes its enthusiasm and the hope these trials represent for NSCLC patients and the oncology community. Acclaim-1 will be used to identify the REQORSA and Tagrisso combination clinical trial, and Acclaim-2 will be used to identify the REQORSA and Keytruda combination clinical trial.

“We are enthusiastically preparing for our upcoming clinical trials and are excited to launch the adoption of this branding,” said Rodney Varner, President and Chief Executive Officer of Genprex. “We believe the Acclaim brand communicates our passion for providing hope to NSCLC patients for important new treatment options in the fight against this devastating disease and aligns us with the clinical, medical and patient communities.”

The trial brand was developed in order to encourage early exposure of the Company’s clinical programs to the broad audience that Genprex’s business addresses, including patients, healthcare practitioners, clinical investigators, investors, employees and others. Genprex plans to initiate the Acclaim-1 clinical trial and the Acclaim 2 clinical trial in the first-half of 2021. Acclaim-1 is a Phase 1/2 clinical trial using a combination of REQORSA with Tagrisso in patients with late stage NSCLC with mutated epidermal growth factor receptors (“EGFRs”) whose disease progressed after treatment with Tagrisso. Acclaim-2 is a Phase 1/2 clinical trial using a combination of REQORSA with Keytruda in NSCLC patients who are low expressors (1 to 49%) of the protein, programmed death-ligand 1 (PD-L1).

About Genprex, Inc.

Genprex, Inc. is a clinical-stage gene therapy company focused on developing potentially life-changing therapies for patients with cancer and diabetes. Genprex’s technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. The Company’s lead product candidate, REQORSA™ (quaratusugene ozeplasmid), is being evaluated as a treatment for non-small cell lung cancer (NSCLC). REQORSA has a multimodal mechanism of action that has been shown to interrupt cell signaling pathways that cause replication and proliferation of cancer cells; re-establish pathways for apoptosis, or programmed cell death, in cancer cells; and modulate the immune response against cancer cells. REQORSA has also

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Higher Donor BMI Tied to Improved Lung Transplant Survival

Lung transplant patients who received a lung from obese donors had a 15-20% reduction in mortality at 1 year in one of the first studies to examine the impact of donor body mass index (BMI) and post-transplant survival.

Findings from the retrospective trial, which included data on patients and donors registered with the United Network for Organ Sharing Standard Transplant and Analysis database, suggest that donor obesity may confer a protective benefit for transplanted lungs.

The findings were presented this week in a poster session at the virtual CHEST conference, the annual meeting of the American College of Chest Physicians.

The BMI of lung transplant recipients has been shown to be an independent predictor of mortality, with studies showing an increased risk of death following transplant in patients who are either underweight or overweight, said Sung Choi, MD, of Rutgers New Jersey Medical School in Newark, who presented the findings.

For example, in a 2017 study involving over 17,000 lung transplants performed in the U.S. from 2005 to 2016, underweight and overweight lung recipients (i.e., BMI ≤20 and ≥28 at the time of listing) were found to be at increased risk for both short- and long-term mortality.

Recipient weight-loss prior to lung transplantation was also associated with a reduction in mortality and days on mechanical ventilation in a 2015 study, with greater reductions in BMI associated with greater survival benefit.

And, in a 2014 consensus statement, the International Society for Heart and Lung Transplantation recommended that a BMI of 30 or greater be considered a relative contraindication to lung transplantation.

Regarding donor BMI, however, Choi told MedPage Today that there hasn’t been prior research examining the impact on lung recipient outcomes and that the findings from his team’s study were a surprise: “We really weren’t expecting this result,” he said.

“We thought greater donor BMI might be associated with an increase in recipient mortality or maybe a null finding. What we found was striking to us. There appeared to be a dose-dependent relationship, with higher donor BMI associated with lower recipient mortality at 90 days and 1 year after the transplant,” Choi said.

Close to 16,000 adult patients who received single- or double-lung transplants from 2005 to 2018 were included in the analysis. Median age of the lung recipients was 59, and roughly 60% were male. Donors were categorized as underweight (BMI <18.5), normal weight (18.5 to <25), overweight (25 to <30), class I obesity (30 to <35), class II obesity (35 to <40), and class III obesity (≥40.0).

Average donor BMI was 25.9, and 45% were classified as normal weight.

A survival benefit at 1 year was observed among patients who received a lung transplant from donors in obesity class 1 (HR 0.867, 95% CI 0.772-0.975, P<0.01) and obesity classes II/III (HR 0.804, 95% CI 0.688-0.941, P<0.01) compared with lungs from normal-weight donors, the researchers reported.

In adjusted analyses, the team reported lower odds of survival with increased donor age, male sex, and presence of diabetes.

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Radiomics Could Help ID Lung Cancer Prognosis After Screening

A model incorporating volume doubling time (VDT) and select radiomic features was able to predict tumor behavior for screen-detected lung cancers, an analysis of low-dose CT (LDCT) scans from the National Lung Screening Trial (NLST) showed.

Using a VDT of 234 days and radiomic features of compactness and average concurrence, very high-risk patients had a 5-year overall survival (OS) of 21.4%, compared with 82.4% for the low-risk group (P<0.0001), reported Jaileene Pérez-Morales, PhD, of Moffitt Cancer Center in Tampa, Florida.

The model also “identified a vulnerable group of early-stage lung cancer patients who had a high risk of experiencing poor survival outcomes,” she said during her presentation at the virtual North America Conference on Lung Cancer.

For this group, the decision tree was able to discriminate between high-risk tumors with a 5-year OS of 39.9%, and more indolent tumors with a 5-year OS of 80.8% (P<0.0001).

“Use of volume doubling time was a hallmark of the NELSON study,” noted discussant Betty Tong, MD, MHS, of Duke University Medical Center in Durham, North Carolina.

“In the study protocol, a volume doubling time of less than 400 days was considered to be positive,” she said. “In contrast to the current study, the NELSON authors determined that the volume doubling time in later rounds of screening was more variable, and that decreasing the volume time less than 400 days was not recommended in later screening rounds.”

For their study, Pérez-Morales and colleagues used LDCT scans from NLST involving 88 patients with malignancy at first follow-up to generate radiomic features that could help classify risk. Participants in the trial underwent three LDCT scans — at baseline and years 1 and 2. A decision-tree analysis was developed to stratify patients into four risk groups (low, intermediate, high, and very high), which showed differences in both progression-free survival (PFS) and OS.

“We also noticed that more aggressive VDTs occurred in the later screening follow-up than the first follow-up,” said Pérez-Morales. “These high-risk patients may require aggressive follow-up and/or adjuvant therapy to mitigate their poor outcomes.”

As VDT requires temporal imaging, the researchers also looked at whether radiomics features could identify high-risk tumors from an initial LDCT scan, and found that two peritumoral features (non-uniformity in Gray level size zone [GLSZM] and average 3D run length) were both predictive of VDT.

“The authors are no strangers to the use of radiomics in lung cancer screening,” Tong noted, pointing to a recently published paper from the group that examined radiomic features of non-small cell lung nodules in the NLST dataset. Again, they created a risk classification system for patients and showed significant differences in PFS and OS between low-, intermediate-, and high-risk groups.

“Even more interesting was the radio-genomic analysis that was performed using a separate dataset of resected tumors and their associated scans — there were differential levels of gene expression associated with select radiomic features,” said Tong.

“One can imagine a possible future state where volume doubling time, radiomics, and even radio-genomics

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Biodesix Announces Data from Three Studies on Lung Nodule Diagnosis and Management to be Shared at CHEST Annual Meeting 2020

Research Evaluates Risk Classification for Patients with Lung Nodules

Biodesix, Inc. a leading data-driven diagnostic solutions company with a focus in lung disease, recently published data from three clinical studies, which found important new information on diagnosis and management of lung nodules. Data from these studies, which are being presented at the American College of Chest Physicians (CHEST) annual meeting, demonstrate the value of the Nodify Lung™ testing strategy and confirm previously reported performance of the Nodify XL2® and Nodify CDT™ tests.

Abstract #A1464/Poster #P1319: Identification of Likely Malignant Indeterminate Pulmonary Nodules by Analysis of Autoantibodies Against Lung Cancer-Associated Antigens
Authors: Kevin Doubleday, James Jett, Laura Peek, Trevor Pitcher
A retrospective analysis of the PANOPTIC study found that the blood-based Nodify CDT test accurately identified patients whose lung nodules were likely malignant, which confirms previously reported test performance. Patients identified as Nodify CDT positive may benefit from a more rapid evaluation and intervention for cancer.

Abstract #A1468/Poster #P1325: Lung Nodule Integrated Classifier Biomarker: First Data with Real-World Clinical Use
Authors: James Jett, Kerstin Pohl, Gerard Silvestri, Steven Springmeyer
A real-world clinical use study demonstrates the utility of the blood-based Nodify XL2 test for identifying patients with likely benign lung nodules by integrating the patients’ blood-based protein data with clinical risk factors, resulting in a large proportion of low to moderate risk nodules being reclassified as very low risk. Risk reclassification can reduce invasive procedures on benign nodules and ultimately lead to improved nodule management.

Abstract #A1476/Poster #P1324: Use of Two Blood-Based Biomarker Tests in Series to Reclassify Risk of Indeterminate Pulmonary Nodules
Authors: Kevin Doubleday, James Jett, Laura Peek, Trevor Pitcher, Steven Springmeyer
Data suggest that while standard risk assessment for lung cancer is imprecise, it can be improved with the blood-based Nodify Lung testing strategy. By combining the Nodify CDT and Nodify XL2 tests, patients can be more appropriately assessed for risk of malignancy to help reduce unnecessary procedures on patients with benign nodules and delays in treatment for patients with cancer.

About Biodesix
Biodesix is a leading diagnostic company with a focus in lung disease. The Company develops diagnostic tests addressing important clinical questions by combining multi-omics through the power of artificial intelligence. Biodesix is the first company to offer six non-invasive tests for patients with diseases of the lung. Biodesix launched the SARS-CoV-2 ddPCR™ test and the Platelia SARS-CoV-2 Total Ab in response to the global pandemic and virus that impacts the lung and causes COVID-19. The blood-based Biodesix Lung Reflex® strategy for lung cancer patients integrates the GeneStrat® and VeriStrat® tests to support treatment decisions with results in 72 hours, expediting time to treatment. The blood-based Nodify Lung™ nodule risk assessment testing strategy, consisting of the Nodify XL2™ and the Nodify CDT™ tests, evaluates the risk of malignancy in incidental pulmonary nodules, enabling physicians to better triage patients to the most appropriate course of action. Biodesix also collaborates with many of the world’s leading biotechnology and pharmaceutical companies to solve complex diagnostic challenges

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Rush Limbaugh says lung cancer has shown progression ‘in the wrong direction’

Conservative talk radio show host Rush Limbaugh says he’s had a setback in his fight against advanced lung cancer.

Limbaugh, 69, said recent scans show “some progression of cancer.” It’s “not dramatic, but it is the wrong direction,” he told listeners Monday, according to a transcript posted on his website.

The host said Monday that he has been diagnosed with stage 4 lung cancer.

On Feb. 3, he first disclosed that he was sick. The following day, President Donald Trump awarded Limbaugh the Presidential Medal of Freedom, the nation’s highest civilian honor, during the State of the Union address.

Limbaugh said that he had been reluctant to speak too much about his illness on-air, in part because “I’m not the only one that’s going through hardships, challenging times.”

“I want to stress here that I know countless numbers of you are experiencing the same thing. If it isn’t lung cancer, it’s some kind of cancer. If it isn’t you, it’s somebody really close to you. If it isn’t an illness, it’s something,” he said Monday.

Limbaugh said that prior to the recent scans that showed some progression, “the scans had shown that we had rendered the cancer dormant.”

“So we have to tweak the treatment plan, which we did, and the chemotherapy drugs in hopes of keeping additional progression at bay for as long as possible,” Limbaugh said. “The idea now is to keep it where it is or maybe have it reduce again. We’ve shown that that is possible.”

This story originally appeared on NBCNews.com.

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Ultimovacs Announces Updated Positive Results from Phase I Trial Evaluating Universal Cancer Vaccine, UV1, in Non-Small Cell Lung Cancer

Ultimovacs ASA (“Ultimovacs”, ticker ULTIMO), today announced five-year overall survival data from the Phase I trial evaluating UV1 as maintenance therapy in patients with non-small cell lung cancer. The results confirm achievement of the primary endpoints of safety and tolerability and indicate encouraging initial signals of long-term survival benefit.

“Ultimovacs has established a growing body of clinical data demonstrating a strong safety and tolerability profile for UV1 and a range of preliminary efficacy signals in several cancer indications, all of which supports the further development of our proprietary cancer vaccine candidate,” stated Carlos de Sousa, Chief Executive Officer at Ultimovacs. “The long-term follow-up results announced today demonstrate that treatment with UV1 is safe both at the time of administration and throughout the follow-up period of at least 5 years. Non-small cell lung cancer highly expresses telomerase and remains an indication in great need of new treatment options for patients.”

In the study, a total of 18 non-small cell lung cancer patients whose disease had not progressed after receiving at least 2nd line treatment with chemotherapy were enrolled to receive UV1 monotherapy as maintenance treatment. Outcomes of the study included the safety and tolerability of UV1 as well as initial signs of clinical response. As per the cut-off date of June 2020, every patient in the trial reached at least 60-months of follow-up post treatment with UV1. At the five-years landmark, the Overall Survival (OS) rate was 33% and median Progression Free Survival (mPFS) was 10.7 months. Throughout the follow-up period, none of the patients experienced unexpected safety issues related to UV1. Further, none of the patients alive after 5 years have received other immunotherapy after the vaccination with UV1.

“At the time of the study initiation, there were no checkpoint inhibitors available for treatment of this patient population. For patients that received a second-line of chemotherapy the expected 5-year survival rate was less than 5 percent,” stated Jens Bjørheim, Chief Medical Officer at Ultimovacs. “While our Phase I study is non-randomized and conducted in a small population, it is promising to see that UV1 was safe and well-tolerated and that using UV1 as a maintenance therapy could potentially provide benefit to patients in need of novel approaches.”

Ultimovacs presented 48-months of follow-up data at the Society for Immunotherapy of Cancer’s (SITC) 34th Annual Meeting in November of last year.

About UV1

UV1 is a peptide-based vaccine inducing a specific T cell response against the universal cancer antigen telomerase. UV1 is being developed as a therapeutic cancer vaccine which may serve as a platform for use in combination with other immunotherapy which requires an ongoing T cell response for their mode of action. To date, UV1 has been tested in four phase I clinical trials in a total of 82 patients and maintained a positive safety and tolerability profile as well as encouraging signals of efficacy.

About UV1 Clinical Programs

As a universal cancer vaccine, UV1’s unique mechanism of action has the potential to

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