Synthetic, Tumor-Targeting Molecule Promotes Immune Activation

Activating the immune system at the site of a tumor can recruit and stimulate immune cells to destroy tumor cells. One strategy involves injecting immune-stimulating molecules directly into the tumor, but this method can be challenging for cancers that are not easily accessible. Now, Stanford researchers have developed a new synthetic molecule that combines a tumor-targeting agent with another molecule that triggers immune activation. This tumor-targeted immunotherapy can be administered intravenously and makes its way to one or multiple tumor sites in the body, where it recruits immune cells to fight the cancer.
Three doses of this new immunotherapy prolonged the survival of six of nine laboratory mice with an aggressive triple negative breast cancer. Of the six, three appeared cured of their cancer over the duration of the monthslong study. A single dose of this molecule induced complete tumor regression in five of 10 mice. The synthetic molecule showed similar results in a mouse model of pancreatic cancer.

An immunotherapy molecule administered intravenously to mice was shown to target tumors.

We essentially cured some animals with just a few injections,” said Jennifer Cochran, PhD, the Shriram Chair of the Department of Bioengineering. “It was pretty astonishing. When we looked within the tumors, we saw they went from a highly immunosuppressive microenvironment to one full of activated B and T cells — similar to what happens when the immune-stimulating molecule is injected directly into the tumor. So, we’re achieving intra-tumoral injection results but with an IV deliver.”

A paper describing the study published online in Cell Chemical Biology.  The lead authors are Stanford graduate student Caitlyn Miller and instructor of medicine Idit Sagiv-Barfi, PhD.

Source: https://med.stanford.edu/

Microrobot Fish Swims Through the Body to Vomit Drugs on cancer

Delivering chemotherapy drugs directly to cancers could help reduce side effects, and soon that job could be done by tiny 3D-printed robotic animals. These microrobots are steered by magnets, and only release their drug payload when they encounter the acidic environment around a tumor.

A new microrobot fish could one day swim through the body with a mouthful of drugs, and automatically spit them up when it encounters cancer cells

The new microrobots are made of hydrogel 3D printed into the shape of different animals, like a fish, a crab and a butterfly, with voids that can carry particles. The team adjusted the printing density in specific areas, like the edges of the crab’s claws or the fish’s mouth, so that they can open or close in response to changes in acidity. Finally, the microrobots were placed in a solution containing iron oxide nanoparticles to make them magnetic.

The end result was microrobots that could be loaded up with drug nanoparticles and steered towards a target location using magnets, where they would release their payload automatically due to changes in pH levels.

In lab tests, the researchers used magnets to guide a fish microrobot through simulated blood vessels, towards a cluster of cancer cells at one end. In that area, the team made the solution slightly more acidic and the fish opened its mouth and spat out the drugs on cue, killing the cancer cells. In other tests, crab microrobots could be made to clasp drug nanoparticles with their claws, scuttle to a target location, and release them.

Source: https://newatlas.com/

Blood Iron Levels Are Key To Slowing Ageing

Genes that could help explain why some people age at different rates to others have been identified by scientists. The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer. The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.

Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageinglifespan, years of life lived free of disease (healthspan), and being extremely long–lived (longevity). Biological ageing – the rate at which our bodies decline over time – varies between people and drives the world’s most fatal diseases, including heart disease, dementia and cancers. The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people. The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing. The researchers confirmed this using a statistical method – known as Mendelian randomisation – that suggested that genes involved in metabolising iron in the blood are partly responsible for a healthy long life.

Blood iron is affected by diet and abnormally high or low levels are linked to age-related conditions such as Parkinson’s disease, liver disease and a decline in the body’s ability to fight infection in older age. The researchers say that designing a drug that could mimic the influence of genetic variation on iron metabolism could be a future step to overcome some of the effects of ageing, but caution that more work is required.

Anonymised datasets linking genetic variation to healthspan, lifespan, and longevity were downloaded from the publicly available Zenodo, Edinburgh DataShare and Longevity Genomics servers.

We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet has been linked to age-related conditions such as heart disease”, said Dr Paul Timmers from the Usher Institute.

The study was funded by the Medical Research Council and is published in the journal Nature Communications.

Source: https://www.ed.ac.uk/

Super-powered Immune Cells Kill Cancer

Ground-breaking immune therapy promises to deliver vital evidence in the fight against cancer as researchers from the Centre for Cancer Biology in Australia open a new clinical trial using genetically engineered immune cells to treat solid cancers. The phase 1 clinical trial will test the feasibility and safety of CAR-T cellsgenetically modified white blood cells harvested from a patient’s own blood with the unique ability to directly attack and kill cancers – to treat advanced solid tumours including small cell lung cancer, sarcomas and triple negative breast cancer.

The new clinical trial will allow researchers to learn more about how CAR-T cells interact with solid tumours in the hope that this form of immune-based therapy may one day treat a wide range of different cancers. Led by the Centre for Cancer Biology – an alliance between University of South Australia (UniSA), the Central Adelaide Local Health Network (CALHN) and the Royal Adelaide Hospital, the trial is funded by Cancer Council’s Beat Cancer Project and sponsored by CALHN.

The research scientist in charge of manufacturing the CAR-T cell product and following the patients’ responses to treatment is UniSA’s Dr Tessa Gargett, a Cancer Council Beat Cancer Project Early Career Fellow from the Centre for Cancer Biology .She says the CAR-T immune therapy shows great potential for developing cancer treatments.

Chimeric antigen receptor (CAR) T cells are a promising new technology in the field of cancer immunotherapy,” Dr Gargett says. “Essentially, CAR-T cells are super-powered immune cells which work by enlisting and strengthening the power of a patient’s immune system to attack tumours. “They’ve had astounding results in treating some forms of chemotherapy-resistant blood cancers, but similar breakthroughs are yet to be achieved for solid cancers – that’s where this study comes in.”

Source: https://www.unisa.edu.au/

Nanobiochip Detects Minute Levels Of Disease

The difficulty in spotting minute amounts of disease circulating in the bloodstream has proven a stumbling block in the detection and treatment of cancers that advance stealthily with few symptoms. With a novel electrochemical biosensing device that identifies the tiniest signals these biomarkers emit, a pair of NJIT inventors are hoping to bridge this gap. Their work in disease detection is an illustration of the power of electrical sensing – and the growing role of engineers – in medical research.

Ideally, there would be a simple, inexpensive test – performed at a regular patient visit in the absence of specific symptoms – to screen for some of the more silent, deadly cancers,” says Bharath Babu Nunna, a recent Ph.D. graduate who worked with Eon Soo Lee, an assistant professor of mechanical engineering, to develop a nanotechnology-enhanced biochip to detect cancers, malaria and viral diseases such as pneumonia early in their progression with a pin prick blood test.

Their device includes a microfluidic channel through which a tiny amount of drawn blood flows past a sensing platform coated with biological agents that bind with targeted biomarkers of disease in body fluids such as blood, tears and urine – thereby triggering an electrical nanocircuit that signals their presence. In research recently published in Nano Covergence, Nunna and his co-authors demonstrated the use of gold nanoparticles to enhance the sensor signal response of their device in cancer detection, among other findings.

One of the device’s core innovations is the ability to separate blood plasma from whole blood in its microfluidic channels. Blood plasma carries the disease biomarkers and it is therefore necessary to separate it to enhance the “signal to noise ratio” in order to achieve a highly accurate test. The standalone device analyzes a blood sample within two minutes with no need for external equipment.

Our approach detects targeted disease biomolecules at the femto scale concentration, which is smaller than nano and even pico scale, and is akin to searching for a planet in a galaxy cluster. Current sensing technology is limited to concentrations a thousand times larger. Using a nanoscale platform allows us to identify these lower levels of disease,” Nunna says, adding, “And by separating the plasma from the blood, we are able to concentrate the disease biomarkers.”

Source: https://www.eurekalert.org/