Monash Biomedicine Develops New Approach for Bolstering T-Cells Ability to Fight Cancer

Credit: CC0 Public Domain

A collaborative study led by the Monash Biomedicine Discovery Institute (BDI) has discovered a new immune checkpoint that may be exploited for cancer therapy

The study shows that by inhibiting the protein tyrosine phosphatase PTP1B in T cells, the body’s immune response to cancer can be mobilized, helping to repress tumor growth.

T cells are an essential part of the body’s immune system, helping not only to kill invading pathogens, such as viruses but also cancer cells. However, this study has shown that the abundance of PTP1B in T cells that infiltrate tumors is increased, thereby restraining the ability of T cells to attack tumor cells and combat cancer. These findings have identified PTP1B as an intracellular brake, or checkpoint, reminiscent of the cell surface checkpoint PD-1—the blockade of which has revolutionized cancer therapy. 

The findings are published in the prestigious journal Cancer Discovery.

Using mice, scientists from Monash BDI, in conjunction with colleagues at the Peter MacCallum Cancer Center in Melbourne and Cold Spring Harbor Laboratory in New York, found that by inhibiting PTP1B, using an early-stage injectable drug candidate that has previously been shown to be safe and well-tolerated in humans, the cancer-fighting ability of T cells is enhanced, repressing tumor growth.

Remarkably, the authors showed that the inhibition of this intracellular checkpoint, PTP1B, can also enhance the response to a widely used cancer therapy that blocks the PD-1 checkpoint on the surface of T cells.

Senior author Professor Tony Tiganis says that although the blockade of PD-1 can be highly effective against many tumors, not all patients respond and the development of resistance is common. This is true even for immunotherapy-sensitive cancers, such as melanoma. Approaches that can enhance the effectiveness or extend the utility of PD-1 checkpoint blockade are highly sought after in the clinic.

“While more pre-clinical work is needed, our findings show that superior outcomes were achieved when we combined PTP1B inhibition with existing immunotherapies in mice,” said Professor Tiganis.

In addition, beyond enhancing the response to PD-1 blockade, the authors showed that the inhibition of PTP1B also significantly enhanced the effectiveness of cellular therapies using Chimeric Antigen Receptor (CAR) T cells.

CAR T cells are T cells derived from a patient’s blood that are modified in the lab so that they produce a man-made receptor to help them better identify tumor cells and then injected back into the patient. 

CAR T cells have been highly effective against some blood cancers; however, this success has not, as yet, been replicated in solid tumors. The authors demonstrate that the deletion or inhibition of PTP1B can dramatically enhance the ability of CAR T cells to attack solid tumors in mice, including breast cancer. 

“To advance this work, a key next step will be to further define the impact of PTP1B deletion in CAR T and conventional T cells in humans. There remains an urgent clinical need to identify and validate cellular targets to revive and sustain T cell responses in cancer,” said first author Dr. Florian Wiede.

Professor Tiganis and Dr. Wiede will also continue to collaborate with Cold Spring Harbor Laboratory and DepYmed Inc., a US-based company developing PTP1B inhibitors, to test in their preclinical models orally bioavailable PTP1B inhibitor drug candidates as novel checkpoint inhibitors. These findings could form the basis of future clinical trials.

Cancer continues to be a major cause of illness and death in Australia, accounting for 30 percent of all deaths in Australia in 2020. The AIHW cancer in Australia report estimates that around 185,000 cases of cancer will be diagnosed in 2031 and that between 2022 and 2031, a total of around 1.7 million cases of cancer will be diagnosed.

The full paper in Cancer Discoveryjournal is titled “PTP1B is an intracellular checkpoint that limits T cell and CAR T cell anti-tumor immunity.”

Graphene: The Next Tech Revolution?

Published on Sep 25, 2012

http://dailyreckoning.com/graphene

A new groundbreaking material recently discovered has the potential to change the world: Water filtration, cellular and battery technology, aircraft and automotive finishing will never be the same.

 

 

 

 

 

New graphene-based super-capacitors last as long as lead-acid batteries

Researcher from Australia‘s Monash University developed new graphene-based supercapacitors that feature high energy density – in fact about 12 times higher than commercially available capacitors. These supercapacitors last as long as a conventional battery (lead-acid).

 

 

 

The researchers used an adaptive graphene gel film, developed at Monash in 2012. They used liquid electrolytes to control the spacing between graphene sheets on the sub-nanometre scale. Those electrolytes played a dual role: maintaining the minute space between the graphene sheets and conducting electricity. In this new electrode design, the density is maximized without compromising porosity.

The researchers say that the production process is simple and can be scaled-up cost-effectively.

Source: Monash University

 

New 2-D Material for Next Generation High-Speed Electronics

Jan. 21, 2013 — Scientists at CSIRO and RMIT University have produced a new two-dimensional material that could revolutionise the electronics market, making “nano” more than just a marketing term.

 

 

The material — made up of layers of crystal known as molybdenum oxides — has unique properties that encourage the free flow of electrons at ultra-high speeds.

In a paper published in the January issue of materials science journal Advanced Materials, the researchers explain how they adapted a revolutionary material known as graphene to create a new conductive nano-material.

Graphene was created in 2004 by scientists in the UK and won its inventors a Nobel Prize in 2010. While graphene supports high speed electrons, its physical properties prevent it from being used for high-speed electronics.

The CSIRO’s Dr Serge Zhuiykov said the new nano-material was made up of layered sheets — similar to graphite layers that make up a pencil’s core.

“Within these layers, electrons are able to zip through at high speeds with minimal scattering,” Dr Zhuiykov said.

“The importance of our breakthrough is how quickly and fluently electrons — which conduct electricity — are able to flow through the new material.”

RMIT’s Professor Kourosh Kalantar-zadeh said the researchers were able to remove “road blocks” that could obstruct the electrons, an essential step for the development of high-speed electronics.

“Instead of scattering when they hit road blocks, as they would in conventional materials, they can simply pass through this new material and get through the structure faster,” Professor Kalantar-zadeh said.

“Quite simply, if electrons can pass through a structure quicker, we can build devices that are smaller and transfer data at much higher speeds.

“While more work needs to be done before we can develop actual gadgets using this new 2D nano-material, this breakthrough lays the foundation for a new electronics revolution and we look forward to exploring its potential.”

In the paper titled ‘Enhanced Charge Carrier Mobility in Two-Dimensional High Dielectric Molybdenum Oxide,’ the researchers describe how they used a process known as “exfoliation” to create layers of the material ~11 nm thick.

The material was manipulated to convert it into a semiconductor and nanoscale transistors were then created using molybdenum oxide.

The result was electron mobility values of >1,100 cm2/Vs — exceeding the current industry standard for low dimensional silicon.

The work, with RMIT doctoral researcher Sivacarendran Balendhran as the lead author, was supported by the CSIRO Sensors and Sensor Networks Transformational Capability Platform and the CSIRO Materials Science and Engineering Division.

It was also a result of collaboration between researchers from Monash University, University of California — Los Angeles (UCLA), CSIRO, Massachusetts Institute of Technology (MIT) and RMIT.