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Funding from the Cancer Prevention and Research Institute of Texas (CPRIT), the second largest global public funder of cancer research, will support the majority of the development costs of 186RNL for leptomeningeal metastases.
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Saint Herblain (France), August 18, 2022 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) a specialty vaccine company, today announced that the U.S. Department of Defense (DoD) has decided not to exercise the second option year of the contract1 to supply Valneva’s Japanese encephalitis (JE) vaccine IXIARO®.
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Addex Reports 2022 Half Year and Second Quarter Financial Results and Provides Corporate Update
Oslo, 18 August 2022: Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical stage leader in immune stimulatory vaccines for cancer, has completed treatment of three patients at the highest dose cohort in the phase I TENDU trial without any safety concerns. Based on these results, the company plans to enroll up to three additional patients at the highest dose level.
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Ultimovacs Expands High Dose Cohort Size in TENDU Phase I Prostate Cancer Trial after Safety Review
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A promising method to treat blindness is to implant healthy light-sensitive cells into failing eyes. But these cell therapies which have been in development for at least three decades often fail because the implanted cells die rapidly or fail to incorporate themselves into the eyes. But new stem-cell research could potentially eliminate these roadblocks.
Whats new Experiments with human stem cells and dogs reveal that a cocktail of drugs that suppress the immune system could help implanted cells survive for months. In fact, the implanted cells even began integrating with the eyes, according to a new study published in the journal Stem Cell Reports.
The scientists injected immunosuppressed dogs with advanced stages of inherited retinal degeneration with the precursors to photoreceptor cells coaxed from human stem cells. They found that the immature cells developed into full-grown photoreceptors and that they started to form connections with the dogs neurons. The research offers a critical first step toward using stem-cell therapies to treat eye conditions, including inherited forms of blindness.
HERE'S THE BACKGROUND Genetic cases of blindness often result from problems with the light-sensitive rod and cone cells in the retina, the tissue that lines the inner eyeball. Scientists have had great success in treating some genetic eye conditions using gene therapies, which involve injecting working versions of malfunctioning genes into the eyes photoreceptor cells. But the genes responsible for many genetic cases of blindness remain unknown.
In turn, several forms of genetic blindness have no gene therapy or indeed any therapeutic options. And for some people it is already too late their condition has progressed so far that no photoreceptor cells remain intact, so gene therapy wouldnt have an effect anyway. Instead, regenerative therapies to replace ailing photoreceptors with functional cells could offer another avenue to reversing blindness.
How they did it In the new study, researchers dosed human stem cells with chemicals that coaxed them into forming the precursors of photoreceptor cells. To help track these cells positions over time, the stem cells were genetically modified to generate fluorescent proteins.
The scientists then injected them into the retinas of seven dogs with normal vision and three with advanced stages of inherited retinal degeneration. In the animals, these immature cells matured into photoreceptors.
When the stem cells were injected into the dogs with normal vision, their retinas were still intact, and therefore served as physical barriers that prevented the implanted cells from connecting with neurons in the eyes. But in the dogs with retinal degeneration (for which the treatment is targeted) the injected cells did a much better job migrating into the retina.
Since the canines immune systems would likely recognize the transplanted human cells as foreign entities and attack them, the researchers gave some immunosuppressive drugs.
As expected, injected cell numbers declined substantially in the canines who did not receive the drug cocktail, whereas cell numbers dipped but then kept steady in dogs who did receive the drugs. The cells in the immunosuppressed dogs survived up to five months post-injection. The researchers also detected signs of implanted cells connecting with neurons in the pups eyes.
Its challenging to turn stem cells into photoreceptors and ensure theyre fully integrated into the eye, but researchers hope patients own cells can eventually be used to treat blindness while avoiding adverse immune reactions.dra_schwartz/E+/Getty Images
Why it matters Discovering that human photoreceptor precursor cells could survive and mature into photoreceptor cells after being transplanted into an adult canine retina suggests regenerating a specific layer of the retina the one that contains rod and cone photoreceptors is possible in an adult eye.
This provides hope for being able to treat patients even in adulthood, Beltran says.
Importantly, the dogs used in this study also provide a better picture of how the same therapy might work in humans. Senior study author William Beltran, a veterinary ophthalmologist and vision scientist at the University of Pennsylvania, tells Inverse that dogs are good models for humans in this case for several reasons, ostensibly making translating the research into human bodies later a simpler task.
For one, large animal models with human-size eyes allow scientists to develop the same surgical approaches that may be used in people.
Dogs also receive therapy doses akin to those that would most likely be used in people, and they may experience some of the same immune reactions as we do.
WHAT'S NEXT In the future, the researchers will continue to refine their technique and eventually test whether the dogs experience improved vision due to the implanted cells.
Its still unclear why some implanted cells died within a few days following transplantation even when dogs were given immunosuppressive drugs. The team is investigating this process in hopes that they can try to improve graft survival, Beltran says.
All in all, future cell therapies for retinal degeneration may require immunosuppressive drugs if the donor cells arent genetically identical to the recipient. The best approach to prevent adverse immune reactions without using immunosuppressive drugs would be to inject stem-cell-derived photoreceptors from the patient after theyve been corrected for genetic defects, Beltran says.
Treatments for blindness may soon join the rapidly expanding and extremely expensive category of personalized medicine.
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This breakthrough stem-cell therapy could reverse genetic blindness - Inverse
Cell membrane-coated nanoparticles, applied in targeted drug delivery strategies, combine the intrinsic advantages of synthetic nanoparticles and cell membranes. Although stem cell-based delivery systems were highlighted for their targeting capability in tumor therapy, inappropriate stem cells may promote tumor growth.
Study:Stem cell membrane-camouflaged targeted delivery system in tumor. Image Credit:pinkeyes/Shutterstock.com
A review published in the journalMaterials Today Biosummarized the role of stem cell membrane-camouflaged targeted delivery system in tumor therapy and focused on the underlying mechanisms of stem cell homing toward target tumors. Nanoparticle-coated stem cell membranes have enhanced targetability, biocompatibility, and drug loading capacity.
Furthermore, the clinical applications of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) were investigated as membrane-camouflaged targeted delivery systems for their anti-tumor therapies. In concurrence, the stem cell membrane-coated nanoparticles have immense prospects in tumor therapy.
Cell-based targeted delivery systems have low immunogenicity and toxicity, innate targeting capability, ability to integrate receptors, and long circulation time. Cells such as red blood cells, platelets, stem cells, tumor cells, immune cells, and even viral/bacterial cells can serve as effective natural vesicles.
MSCs derived from the umbilical cord (UC-MSCs), bone marrow (BM-MSCs), and adipose tissue (ATMSCs) are utilized in clinical applications. However, iPSCs are preferable over MSCs in clinical applications due to their easy fetch by transcription factor-based reprogramming of differentiation of somatic cells.
Stem cells (MSCs/ iPSCs) can be easily isolated and used as drug delivery systems for tumor therapy. Stem cell-based delivery systems have inflammation or tumor lesions targeting capacity. However, stem cells are often entrapped in the lung due to their size, resulting in microembolism.
Cell membrane-coated nanoparticles are applied in targeted delivery strategies. To this end, stem cell membrane-coated nanoparticles have tremendous prospects in biomedical applications. Although previous reports mentioned the role of cell membrane-coated nanocarriers in tumor therapy, delivery systems based on stem cell membranes have not been explored extensively.
Stem cell membrane-coated nanoparticles obtained from stem cells have complex functioning and can achieve biological interfacing. Consequently, stem cell membrane-coated nanoparticles served as novel drug delivery systems that could effectively target the tumor.
Previous reports mentioned the preparation of doxorubicin (DOX) loaded, poly (lactic-co-glycolic acid) (PLGA) coated MSC membrane-based nanovesicles, which showed higher cellular uptake than their PLGA uncoated counterparts. Similarly, the DOX-loaded MSC membrane-coated gelatin nanogels showed enhanced storage stability and sustained drug release.
Thus, the stem cell membrane-coated nanoparticles served as novel carriers for stem cells and facilitated the targeted delivery of the drugs at the tumor site. Since the stem cell membrane-coated nanoparticles had good targeting and penetration abilities, they enhanced the efficiency of chemotherapeutic agents in tumor therapy and minimized the side effects.
Reactive oxygen species (ROS) based photodynamic therapy (PDT) is mediated by photosensitizers with laser irradiations. Previous reports mentioned the development of MSC membrane-based mesoporous silica up-conversion ([emailprotected]2) nanoparticles that efficiently targeted the tumor due to their high affinity after being coated with MSC membrane.
These cell membrane-coated nanoparticles showed high cytocompatibility (with hepatocyte cells) and hemocompatibility (with blood). Moreover, the [emailprotected]2 nanoparticles-based PDT therapy under 980-nanometer laser irradiations could inhibit the tumors in vivo and in vitro. Consequently, the stem cell membrane-coated nanoparticles had circulation for an extended time and escaped the immune system, thereby increasing their accumulation at the tumor site.
Stem cell membrane-coated nanoparticles were also applied to deliver small interfering RNA (siRNA) via magnetic hyperthermia therapy and imaging. Previous reports mentioned the preparation of superparamagnetic iron oxide (SPIO) nanoparticles using an MSC membrane that reduced the immune response.
Additionally, the CD44 adhesion receptors were preserved on the surface of the MSC membrane during preparation. These prepared nanovesicles were unrecognized by macrophages, which enabled their stability in blood circulation. The nanosize and tumor homing capacity of MSCs helped the nanovesicles generate a dark contrast in T2-weight magnetic resonance imaging (MRI).
Cell membrane-coated nanoparticles helped fabricate various targeted delivery strategies. Especially, stem cell membrane-coated nanoparticles have the following advantages: stem cells are easy to isolate and expand in vitro. Thus, multilineage potential and phenotypes could be preserved for more than 50 population doublings in vitro.
Stem cell membrane-coated nanoparticles also have an intrinsic capacity to target inflammation or tumor lesions. Hence, these nanoparticles were established for tumor therapy, building a strong foundation for stem cell membrane-mediated delivery systems.
On the other hand, stem cell membrane-coated nanoparticles have the following drawbacks: Despite various sources for collecting MSCs (UC-MSCs/BM-MSCs/ATMSCs), the number of cells obtained is limited, although iPSCs are relatively easy to fetch by reprogramming differentiated somatic cells, the reprogramming is a high-cost step, restricting the clinical applications of iPSCs.
Zhang, W., Huang, X. (2022). Stem cell membrane-camouflaged targeted delivery system in tumor. Materials Today Bio.https://www.sciencedirect.com/science/article/pii/S2590006422001752
Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.
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Stem Cell Membrane-Coated Nanoparticles in Tumor Therapy - AZoNano