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Destroying tumors in mice; de-aging fruit flies; counting neurons in zebrafish

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Destroying tumors in mice; de-aging fruit flies; counting neurons in zebrafish

This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

Improving cancer immunotherapy in mice

SNL Image

Scientists increased the destruction of tumor tissue in mice by combining multiple antibodies.
Source: Pixabay

Scientists with the University of Basel improved the destruction of tumors in mice by combining multiple antibodies in cancer immunotherapy treatment — and actually improving the health of the tumor to allow the medicines to attack the diseased tissue.

Cancer immunotherapies use the body's immune system to destroy cancer tissues. An antibody that activates the CD40 receptor, which generates the production of killer T-cells, appeared to be an effective therapy in preclinical studies; however, it proved less effective in further trials, according to a Dec. 30, 2019, press release from the University of Basel.

The research team found that the anti-CD40 antibody was producing killer T-cells, but not penetrating deep into the tumor because the tumor's blood vessels were not healthy.

After combining the anti-CD40 antibody with two antibodies to stabilize the tumor's blood vessels, the treatment was able to penetrate further into the tumor and increase destruction of the tissue.

One antibody used was Avastin from Roche Holding AG's Genentech, which has already been approved for cancer treatment, and the other antibody is still in clinical development, according to the University of Basel. Roche provided all antibodies for the study.

The therapy was tested in mice with colorectal, breast and skin cancer, and the therapy improved tissue destruction in all cancer forms.

Researchers believe the new treatment technique could be beneficial for patients who have not responded to previous immunotherapy treatments. The study was published Dec. 30, 2019, in Proceedings of the National Academy of Sciences.

Renewed life for middle-aged fruit flies

Researchers with Iowa State University have restored function and strength to cardiac muscles in middle-aged fruit flies, which may open the door to targeted drug development for humans, according to a study published Dec. 29, 2019, in the academic journal Autophagy.

By boosting a pathway linked to the aging of tissues, scientists were able to restore heart function in a five to six week old fruit fly to that of a one to two week old bug.

For the experiment, the research team focused on the mechanistic target of rapamycin, or mTOR, a pathway linked to autophagy that helps balance organism growth and nutritional intake in nearly all organisms, according to a Jan. 7 press release from Iowa State University. Autophagy is a cellular process that removes damaged cells. The process declines with age and can cause cardiac muscles to weaken.

The team strengthened the heart muscles of aging fruit flies by boosting one of the two complexes that make up the mTOR pathway, called mTORC2, which decreases with age as autophagy also declines, according to the press release. To make their observations of cardiac activity, researchers used thousands of high-resolution video recordings of cardiac muscles in flies of various ages.

Hua Bai, lead researcher on the study and assistant professor of genetics, development and cell biology at Iowa State University, said the "fly model can be useful for developing drug target discoveries that could have a big impact on human health."

This is not the only Fountain of Youth-related discovery that has come from studying the humble fruit fly. A study published in Proceedings of the National Academy of Sciences in September 2019 found that a triple-drug combination treatment extended the lifespan of the species.

Zebrafish > all other fish

SNL ImageScientists believe understanding how zebrafish regenerate neurons could help treat humans with neurodegenerative diseases.
Source: Thinkstock

Scientists with the German research institute Technische Universität Dresden identified which neurons in zebrafish were newly regenerated and the total number of new neurons, according to a research article published Jan. 6 in the research journal Development.

Zebrafish are able to reproduce neurons if they are damaged due to injury or disease and integrate those neurons into their nervous system, according to a Jan. 7 press release from the university.

The research team was able to identify both newly formed projection neurons and internal neurons in the forebrain of transgenic zebrafish. Projection neurons create a connection in different brain areas, while internal neurons strengthen the activity of projection neurons, according to the press release.

The study's findings are encouraging for future human therapies because the great fish has the same types of brain cells as humans.

"We hope to gain insights that are relevant for possible therapies helping people after injuries and strokes or suffering from neurodegenerative diseases," Michael Brand, senior author on the study, said in the statement. "We already know that a certain regenerative ability is also present in humans and we are working on awakening this potential."