New combination treatment could help fight advanced melanoma

A study by researchers at the UCLA Jonsson Comprehensive Cancer Center suggests that using an immunotherapy drug called NKTR-214, also known as bempegaldesleukin, in combination with an infusion of anti-tumor immune cells, or T cells, may produce a stronger immune response that could help fight advanced melanoma.

When tested in mice with melanoma tumors that were unlikely to stimulate an immune response, the approach increased the number of anti-tumor immune cells, and those immune cells lived longer and functioned better than the standard therapy, empowering the cells to destroy the tumor.

Background
Adoptive cell therapy is a type of immunotherapy that has had promising results for treating people with advanced cancers. The approach involves extracting and harvesting immune cells from a patient and engineering them in the laboratory to attack specific antigens on the surface of tumors. One challenge is that it requires giving patients interleukin 2, a protein signaling molecule in the immune system, to promote the development and expansion of the infused immune cells. But interleukin 2 can also activate cells to suppress the immune system, and because it is highly toxic, it can have serious adverse side effects.

Researchers have been seeking ways to produce large number of immune cells without exposing patients to those negative side effects -- including by combining adoptive cell therapy with other treatments.

Method

Researchers used mice to test NKTR-214 in combination with adoptive cell therapy. Using bioluminescence imaging, the researchers tracked the movement of T cells in the mice that received the combination therapy. The team observed an expansion of T cells in the spleen, the organ that helps accelerate the activation and expansion of T cells throughout the body. The T cells then migrated to the tumor, where they continued to have a long-lasting effect. The in vivo expansion and T cell accumulation in tumors was greatly improved when using NKTR-214 compared to using interleukin-2.

Impact
While immunotherapy has changed the face of cancer treatment for people with advanced cancers, it still only works in a small subset of patients. The results of the UCLA study suggest that using NKTR-214 in combination with adoptive cell therapy could be effective for more people with advanced solid tumors.

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Study finds new synthetic vaccines to comabt Chikungunya

Researchers developed a new type of vaccine for mosquito-borne virus Chikungunya. Since the vaccine does not require refrigeration, it is considered a major advancement in vaccine technology.
The findings, revealed exceptionally promising results for the Chikungunya vaccine candidate, which has been engineered using a synthetic protein scaffold that could revolutionise the way vaccines are designed, produced and stored.

Researchers teamed up with IT professionals to find a way to make vaccines that are thermostable ( able to withstand warm temperatures), can be designed quickly and are easily produced.

We were working with a protein that forms a multimeric particle resembling a virus but is completely safe because it has no genetic material inside said an expert virologist. Completely by chance, we discovered that this particle was incredibly stable even after months, without refrigeration.

This particle has a very flexible, exposed surface that can be easily engineered, added  another researcher. We figured that we could insert small, harmless bits of Chikungunya to generate a virus-like mimic we could potentially use as vaccine.

To validate their design, the scientists employed cyro-electron microscopy, a powerful new technique recently installed in Bristol\s state-of-the-art microscopy facility headed by co-author of the study. Cyro-EM yields very large data sets from which the structure if a sample can be determined at near0atomic resolution, requiring massive parallel computing.

Enabled by IT's high-performance cloud infrastructure, the team developed a novel computational approach to create an accurate digital model of the synthetic vaccine.

IT specialists together with colleagues, implemented software packages seamlessly on the cloud in this pioneering effort.

IT professional were able to process a large data sets obtained by the microscope on the clod in a fraction of the time and at a much lower cost than previously thought possible, explained one of the professional.

Researchers have had a long tradition of building and installing their own supercomputers on-premises, but cloud computing is allowing them to run large data sets in record time, with fast connectivity and low latency, added  the leading cloud architect.

This is helping them crunch data and make scientific breakthroughs much faster. Going by forward, technologies like machine learning and cloud computing will play a significant part in the scientific world, and we are delighted we could help the researchers with this important discovery, the professional said.

The particles the scientists designed yielded exceptionally promising results in animal studies, soundly setting the stage for a future vaccine to combat Chikungunya disease.

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New drug proves to be promising for pancreatic cancer

Researchers have invented a new drug for treating pancreatic cancer, which also showed promising initial results.

Radiation and chemotherapy drug gemcitabine, which are the standard treatment for pancreatic cancer, both work by causing damage to DNA. But pancreatic cancer has a way of repairing that damage, which limits how effective these therapies can be.

Researchers found that AZD1775 prevented pancreatic cancer from protecting itself against the effects of radiation and gemcitabine, while leaving normal cells relatively unaffected.

If we can disable the DNA damage response in pancreatic cancer cells, it might eliminate treatment resistance and sensitize cancer to the effects of both radiation and chemotherapy, said an associate Prof. of radiation oncology.

According to the study, the trial enrolled 34 patients with locally advanced pancreatic cancer.
Patients received AZD1775 in addition to radiation and gemcitabine. The goal of the study was to determine the maximum tolerated dose of AZD2775 in this combination. In the process, the researchers also found that this combination resulted in better than expected overall survival.

Pancreatic cancer is particularly known for spreading to distant parts of the body, part of the reason overall 5-year survival is just 9%.

If we're ever going to cure pancreatic cancer, we're going to need effective systemic treatment as well as local therapy. Our data suggest that AZD1775 can do both, said the senior author of the study.
The median overall survival in the study was 22 months, with no progression for a median of 9 months. A previous study using gemcitabine alone in a similar group of patients found an overall survival of 12-14 months.

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Adding AZD1775 to radiation and gemcitabine was relatively well tolerated with encouraging survival results. Further studies with promising combination are needed, the author concluded.

Cancer 'vaccine' shows promise in human trial of lymphoma patients

An experimental cancer "vaccine" showed promising results in a small clinical trial of patients with lymphoma, according to a study.

Researchers tested the treatment in 11 patients with lymphoma. Their results were successful enough to warrant another clinical trial in March on lymphoma patients as well as breast and head-and-neck cancer.

Researchers said some patients in the initial human trial went into full remission for months or even years.

The treatment "has broad implications for multiple types of cancer," said lead author, the director of the lymphoma immunotherapy program. "This method could also increase the success of other immunotherapies such as checkpoint blockade.

They refer to it as a vaccine because it causes a person's immune system to fight the disease, though it's not preventive like the flu shot. In this case, the treatment teaches the body to recognize tumors and attack them.

Researchers created the treatment directly inside the tumor. To do this, they injected one tumor with a stimulant to recruit immune cells, treated the tumor with a low dose of radiation then injected it with a stimulant to activate immune cells. These activated immune cells then travel throughout the body, killing tumors wherever they find them.

In three of the patients, the treatment shrunk not only the tumor that was treated but also other ones throughout the body, putting these patients into remission.

"It's really promising, and the fact you get not only responses in treated areas, but areas outside the field [of treatment with radiation] is really significant," said a Dr. who was not involved in the study and is working on a similar treatment.

While promising, the effect was observed in only three people and will need to be tested in larger trials before even going before the Food and Drug Administration for review.

The Dr. said the results are exciting but cautioned more research needs to be done. 

"It's definitely proof of concept, but larger studies are definitely needed and additional strategies to try to get more than three out of 11 patients to respond," he said,  who is also developing a lymphoma vaccine, though with a slightly different approach.

Researchers for decades have tried but failed to create cancer vaccines. New research on immunotherapy, or training a person's immune system to fight disease, has reinvigorated their efforts.
The vaccine activates dendritic cells, which are responsible for initiating immune responses. These cells then instruct T-cells to attack tumors in a person's body, like generals instructing soldiers how to fight.

"Generals don't really fight wars, they make the plans," the Dr. said.

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