Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New cancer immunotherapy approach turns immune cells into tiny anti-tumor drug factories

05.12.2018

In lab and mouse experiments, UC San Diego School of Medicine researchers developed a method to leverage B cells to manufacture and secrete tumor-suppressing microRNAs

Cancer immunotherapy -- efforts to better arm a patient's own immune system to attack tumors -- has shown great potential for treating some cancers. Yet immunotherapy doesn't work for everyone, and some types of treatment can cause serious side effects.


UC San Diego School of Medicine researchers developed a method to use B cells to manufacture and secrete microRNA-containing vesicles and showed they can inhibit tumor growth in mice.

Credit: UC San Diego Health

In a new approach, researchers at University of California San Diego School of Medicine are turning B cells, best known for producing antibodies, into factories that assemble and secrete vesicles or sacs containing microRNAs. Once internalized by cancer cells, these small pieces of genetic material dampen a gene that spurs tumor growth. In mice, breast tumors treated with this approach were fewer and significantly smaller than in untreated tumors.

The study is published in the December 4 issue of Scientific Reports.

"Once further developed, we envision this method could be used in situations where other forms of immunotherapy don't work," said senior author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at UC San Diego Moores Cancer Center.

"The advantages are that this type of treatment is localized, meaning potentially fewer side effects. It's long-lasting, so a patient might not need frequent injections or infusions. And it would likely work against a number of different tumor types, including breast cancer, ovarian cancer, gastric cancer, pancreatic cancer and hepatocellular carcinoma."

MicroRNAs don't encode proteins. Instead, microRNAs bind messenger RNAs that do encode proteins, inhibiting their translation or hastening their degradation. Normal cells use microRNAs to help fine-tune which genes are dialed up or down at different times. MicroRNAs tend to be less active in cancer cells, which can allow growth-related proteins to run wild.

In this study, Zanetti and team used miR-335, a microRNA that specifically dampens SOX4, a transcription factor that promotes tumor growth. They added a miR-335 precursor to B cells in the lab.

Once inside, through a naturally occurring process, the cells convert the precursor into mature, active miR-335 and package it into vesicles, small, membrane-coated sacs that bud off from the cell. Each B cell can produce 100,000 miR-335-containing vesicles per day -- enough to treat 10 cancer cells.

To test this new system, the researchers treated human breast cancer cells with miR-335-containing vesicles or sham vesicles in the lab. Then they transplanted the cancer cells to mice. After 60 days, 100 percent (5/5) of the mice with mock-treated cancer cells had large tumors. In contrast, 44 percent (4/9) of the mice with miR-335 vesicle-treated cancer cells had tumors. On average, the tumors in the treated mice were more than 260 times smaller than those in the mock-treated mice (7.2 vs. 1,896 mm3).

And the treatment was long-lasting -- miR-335 levels were still elevated in the treated mice 60 days after the vesicles and cancer cells were transplanted.

"We were surprised to find that even small changes in cancer cell gene expression after miR-335 treatment were associated with specific down-regulation of molecules key to tumor growth," said study co-author Hannah Carter, PhD, assistant professor of medicine at UC San Diego School of Medicine.

Other research groups and pharmaceutical companies are using tumor suppressor microRNAs therapeutically. What's new here, said researchers, is the method for producing and delivering them.

According to Zanetti, this therapy could be developed in two ways. First, by first harvesting vesicles from B cells in a lab, then administering only the vesicles, as they did here, or second, by administering the B cells themselves. He says the challenge now will be to develop ways to ensure the B cells or vesicles get as close to a tumor as possible. This would be easier in some types of cancer, where the tumor is readily accessible by injection. But many cancers are difficult to access. Zanetti and colleagues are currently working to improve the delivery system, maximize efficiency and diminish side effects.

"Ideally, in the future we could test patients to see if they carry a deficiency in miR-335 and have an overabundance of SOX4," Zanetti said. "Then we'd treat only those patients, cases where we know the treatment would most likely work. That's what we call personalized, or precision, medicine. We could also apply this technique to other microRNAs with other targets in cancer cells and in other cell types that surround and enable tumors."

###

Other study co-authors are Gonzalo Almanza, Jeffrey J. Rodvold, Brian Tsui and Kristen Jepsen, all at UC San Diego.

Media Contact

Heather Buschman, PhD
hbuschman@ucsd.edu
858-249-0456

 @UCSanDiego

http://www.ucsd.edu 

Heather Buschman, PhD | EurekAlert!

More articles from Health and Medicine:

nachricht Correct antibiotic dosing could preserve lung microbial diversity in cystic fibrosis
22.02.2019 | Children's National Health System

nachricht Researchers find trigger that turns strep infections into flesh-eating disease
19.02.2019 | Houston Methodist

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: (Re)solving the jet/cocoon riddle of a gravitational wave event

An international research team including astronomers from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has combined radio telescopes from five continents to prove the existence of a narrow stream of material, a so-called jet, emerging from the only gravitational wave event involving two neutron stars observed so far. With its high sensitivity and excellent performance, the 100-m radio telescope in Effelsberg played an important role in the observations.

In August 2017, two neutron stars were observed colliding, producing gravitational waves that were detected by the American LIGO and European Virgo detectors....

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Global Legal Hackathon at HAW Hamburg

11.02.2019 | Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

 
Latest News

JILA researchers make coldest quantum gas of molecules

22.02.2019 | Physics and Astronomy

Understanding high efficiency of deep ultraviolet LEDs

22.02.2019 | Materials Sciences

Russian scientists show changes in the erythrocyte nanostructure under stress

22.02.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>