Tag Archives: immunotherapy

Nanoparticle Targets Tumor-infiltrating Immune Cells, Flips Switch Telling Them To Fight

Immunotherapy’s promise in the fight against cancer drew international attention after two scientists won a Nobel Prize this year for unleashing the ability of the immune system to eliminate tumor cells.

But their approach, which keeps cancer cells from shutting off the immune system’s powerful T-cells before they can fight tumors, is just one way to use the body’s natural defenses against deadly disease. A team of Vanderbilt University bioengineers today announced a major breakthrough in another: penetrating tumor-infiltrating immune cells and flipping on a switch that tells them to start fighting. The team designed a nanoscale particle to do that and found early success using it on human melanoma tissue.

Tumors are pretty conniving and have evolved many ways to evade detection from our immune system,” said John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells. “Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies. We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer.

That molecule is called cGAMP, and it’s the primary way to switch on what’s known as the stimulator of interferon genes (STING) pathway: a natural mechanism the body uses to mount an immune response that can fight viruses or bacteria or clear out malignant cells. Wilson said his team’s nanoparticle delivers cGAMP in a way that jump-starts the immune response inside the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.

While the Vanderbilt team’s research focused on melanoma, their work also indicates that this could impact treatment of many cancers, Wilson said, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.

The findings are reported in the journal Nature Nanotechnology.

Source: https://news.vanderbilt.edu/

Better Treat Salmonella Than Face Cancer

An interdisciplinary team of three Virginia Tech faculty members affiliated with the Macromolecules Innovation Institute has created a drug delivery system that could radically expand cancer treatment options. The conventional cancer treatment method of injecting nanoparticle drugs into the bloodstream results in low efficacy. Due to the complexities of the human body, very few of those nanoparticles actually reach the cancer site, and once there, there’s limited delivery across the cancer tissue.

The new system created at Virginia Tech is known as Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS). Researchers have developed a process to chemically attach nanoparticles of anti-cancer drugs onto attenuated bacteria cells, which they have shown to be more effective than the passive delivery of injections at reaching cancer sites.

NanoBEADS has produced results in both in vitro (in tumor spheroids) and in vivo (in living mice) models showing up to 100-fold improvements in the distribution and retention of nanoparticles in cancerous tissues.This is a product of Bahareh Behkam, associate professor of mechanical engineering. Collaborators on this interdisciplinary team are Rick Davis, professor of chemical engineering, and Coy Allen, assistant professor of biomedical sciences and pathobiology in the Virginia-Maryland College of Veterinary Medicine.

You can make the most amazing drugs, but if you cannot deliver it where it needs to go, it cannot be very effective,” Behkam said. “By improving the delivery, you can enhance efficacy.

Humans have noticed, even as far back as Ancient Egypt, that cancer went into remission if the patient also contracted an infection like salmonella. Neither are ideal, but humans can treat salmonella infections more effectively than cancer.

In modern times, Allen said the idea of treating cancer with infections traces back to the late 1800s and has evolved into immunotherapy, in which doctors try to activate the immune system to attack cancerous cells. Of course, salmonella is harmful to humans, but a weakened version could in theory provide the benefits of immunotherapy without the harmful effects of salmonella infection. The concept is similar to humans receiving a weakened flu virus in a vaccine to build immunity.

The work, which combines expertise in mechanical engineering, biomedical engineering, chemical engineering, and veterinary medicine, was recently detailed in Advanced Science.

Source: https://vtnews.vt.edu/

Immunotherapy Technique Specifically Targets Tumor Cells

A new immunotherapy screening prototype developed by University of California, Irvine (UCI) researchers can quickly create individualized cancer treatments that will allow physicians to effectively target tumors without the side effects of standard cancer drugsUCI’s Weian Zhao and Nobel laureate David Baltimore with Caltech led the research team that developed a tracking and screening system that identifies T cell receptors with 100-percent specificity for individual tumors within just a few days.

In the human immune system, T cells have molecules on their surfaces that bind to antigens on the surface of foreign or cancer cells. To treat a tumor with T cell therapy, researchers must identify exactly which receptor molecules work against a specific tumor’s antigens. UCI researchers have sped up that identification process.

This technology is particularly exciting because it dismantles major challenges in cancer treatments,” said Zhao, an associate professor of pharmaceutical sciences. “This use of droplet microfluidics screening significantly reduces the cost of making new cancer immunotherapies that are associated with less systemic side effects than standard chemotherapy drugs, and vastly speeds up the timeframe for treatment.

Zhao added that traditional cancer treatments have offered a one-size-fits-all disease response, such as chemotherapy drugs which can involve systemic and serious side effects.

Research findings appear in Lab on a Chip.

Source: https://news.uci.edu/

Universal Antibody Drug for HIV

A research team led by scientists at AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU) invents a universal antibody drug against HIV/AIDS. By engineering a tandem bi-specific broadly neutralizing antibody, the team found that this novel antibody drug is universally effective not only against all genetically divergent global HIV-1 strains tested but also promoting the elimination of latently infected cells in a humanized mouse model. The new findings are now published in the Journal of Clinical Investigation, one of the world’s leading biomedical journals.

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AIDS remains an incurable disease. In the world, HIV/AIDS has resulted in estimated 40 million deaths while 36.9 million people are still living with the virus.  To end the HIV/AIDS pandemic, it is important to discover either an effective vaccine or a therapeutic cure. There are, however, two major scientific challenges: the tremendous HIV-1 diversity and the antiviral drug-unreachable latency. Since it is extremely difficult to develop an appropriate immunogen to elicit broadly neutralizing antibodies (bnAbs) against genetically divergent HIV-1 subtypes, developing existing bnAbs as passive immunization becomes a useful approach for HIV-1 prophylaxis and immunotherapy.

Previous studies have investigated the potency, breadth and crystal structure of many bnAbs including their combination both in vitro and in vivo. Naturally occurring HIV-1 resistant strains, however, are readily found against these so-called bnAbs and result in the failure of durable viral suppression in bnAb-based monotherapy. To improve HIV-1 neutralization breadth and potency, bispecific bnAb, which blocks two essential steps of HIV-1 entry into target cells, have been engineered and show promising efficacy in animal models. Before the publication, tandem bi-specific bnAb has not been previously investigated in vivo against HIV-1 infection.

Source: https://www.med.hku.hk/

How To Turn On Cancer-Killing Immune Cells

A remote command could one day send immune cells on a rampage against a malignant tumor. The ability to mobilize, from outside the body, targeted cancer immunotherapy inside the body has taken a step closer to becoming reality. Bioengineers at the Georgia Institute of Technology have installed a heat-sensitive switch into T-cells that can activate the T-cells when heat turns the switch on. The method, tested in mice and published in a new study, is locally targeted and could someday help turn immunotherapy into a precision instrument in the fight against cancer.

Immunotherapy has made headlines with startling high-profile successes like saving former U.S. President Jimmy Carter from brain cancer. But the treatment, which activates the body’s own immune system against cancer and other diseases, has also, unfortunately, proved to be hit-or-miss.

In patients where radiation and traditional chemotherapies have failed, this is where T-cell therapies have shined, but the therapy is still new,” said principal investigator Gabe Kwong. “This study is a step toward making it even more effective.”

Cancer is notoriously wily, and when T-cells crawl into a tumor, the tumor tends to switch off the T-cellscancer-killing abilities. Researchers have been working to switch them back on.

Kwong’s remote control has done this in the lab, while also boosting T-cell activity. In the study, Kwong’s team successfully put their remote-control method through initial tests in mice with implanted tumors (so-called tumor phantoms, specially designed for certain experiments).

Source: http://www.rh.gatech.edu/