RNA Technology to Erase Age-related Wrinkles

A team of researchers led by The University of Texas MD Anderson Cancer Center has developed a novel delivery system for messenger RNA (mRNA) using extracellular vesicles (EVs). The new technique has the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies.
In the study, published today in Nature Biomedical Engineering, the researchers use EV-encapsulated mRNA to initiate and sustain collagen production for several months in the cells of photoaged skin in laboratory models. It is the first therapy to demonstrate this ability and represents a proof-of-concept for deploying the EV mRNA therapy.

This is an entirely new modality for delivering mRNA,” said corresponding author Betty Kim, M.D., Ph.D., professor of Neurosurgery. “We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently have no good method for being delivered.
The genetic code for building specific proteins is contained in mRNA but delivering mRNA within the body is one of the largest hurdles facing clinical applications of many mRNA-based therapies. The current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and the other primary delivery systems for genetic materials so far have been viral based. However, each of these approaches comes with certain limitations and challenges.

Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, which gives them the benefit of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Additionally, their size allows them to carry even the largest human genes and proteins.

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‘Drug Factory’ Implants Could Eliminate Specific Lung Cancer

Rice University and Baylor College of Medicine researchers have shown they can seradicate advanced-stage mesothelioma tumor in mice in just a few days with a treatment combining Rice’s cytokinedrug factoryimplants and a checkpoint inhibitor drug.

The researchers administered the drug-producing beads, which are no larger than the head of a pin, next to tumors where they could produce continuous, high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer. The study, published online today in Clinical Cancer Research, is the latest in a string of successes for the drug-factory technology invented in the lab of Rice bioengineer Omid Veiseh, including Food and Drug Administration (FDAapproval to begin clinical trials of the technology this fall in ovarian cancer patients.

From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers,” said Rice graduate student Amanda Nash, who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, a fellow student in Veiseh’s lab.

The cytokine factories consist of alginate beads loaded with tens of thousands of cells that are genetically engineered to produce natural IL-2, one of two cytokines the FDA has approved for treatment of cancer. The factories are just 1.5 millimeters wide and can be implanted with minimally invasive surgery to deliver high doses of IL-2 directly to tumors. In the mesothelioma study, the beads were placed beside tumors and inside the thin layer of tissue known as the pleura, which covers the lungs and lines the interior wall of the chest.

I take care of patients who have malignant pleural mesothelioma,” said Dr. Bryan Burt, professor and chief of Baylor’s Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery. “This is a very aggressive malignancy of the lining of the lungs. And it’s very hard to treat completely by surgical resection. In other words, there is often residual disease that is left behind. The treatment of this residual disease with local immunotherapy — the local delivery of relatively high doses of immunotherapy to that pleural space — is a very attractive way to treat this disease.”

Veiseh said the mesothelioma study began when Burt and Baylor surgeon and associate professor Dr. Ravi Ghanta heard about the early results of ovarian cancer animal tests Veiseh’s team was conducting with collaborators at the University of Texas MD Anderson Cancer Center. In March, Veiseh and MD Anderson collaborators published a study showing IL-2-producing beads could eradicate advanced-stage ovarian and colorectal tumors in mice in less than a week.

They were really impressed by the preclinical data we had in ovarian cancer,” Veiseh said of Burt and Ghanta. “And they asked the question, ‘Could we actually leverage the same system for mesothelioma?’

Source: https://blogs.bcm.edu/

Natural Killer Cells, Primed with an Antibody, Induce Remissions in Patients with Advanced Lymphoma

Two patients with advanced Hodgkin lymphoma were told their tumors were
so resistant to treatment that hospice was their best option. Then, they were
enrolled in a clinical trial of a novel immunotherapy involving so-called
natural killer cells. After treatment, they saw complete remission.
Researchers say the results are a hopeful if preliminary sign of the potential of immunotherapies harnessing natural killer, or NK, cellsinnate immune system cells that have certain advantages over the more commonly recognized adaptive T cell cancer therapies.
The treatment in the study, developed by the University of Texas MD Anderson Cancer Center and the German drug maker Affimed, combined offthe-shelf NK cells with a separate antibody that primes the cells to recognize a specific protein signature of the tumors. Two additional patients administered
the same treatment have shown ongoing partial responses.

These results show you just how powerful NK cells are,” said Katy Rezvani,
a stem-cell transplant physician and NK cell researcher at MD Anderson, who
is spearheading the development of this new treatment.
It’s amazing when you see these responses for patients who have so few
options, patients who’ve been told that they should go to hospice,” Rezvani
said.“I cannot begin to tell you how satisfying this is for clinicians.
Data from the study is to be presented at the annual meeting of the American
Association for Cancer Research (AACR).
Source: https://www.mdanderson.org/
AND
https://www.mskcc.org/