Torque’s T cell ‘backpacks’ may boost immune attack against solid tumors

T-cell therapies like Gilead’s Yescarta and Novartis’ Kymriah have generated enthusiasm because of their high response rates in patients with lymphoma and leukemia. But the technology—which involves removing immune-boosting T cells from patients and then engineering them to recognize and kill cancer—has proven difficult to translate to solid tumors.

Researchers from the Massachusetts Institute of Technology believe they’ve found a solution to that problem: nanoparticle “backpacks” that can be attached to T cells. The backpacks are filled with drugs that stimulate the immune system, and they’re showing promise in mouse studies—so much promise that MIT spinoff Torque Biotherapeutics is now planning clinical trials for the treatment in several tumor types, according to a statement.

The team is applying the new technology to a technique called adoptive T-cell therapy, in which the immune-boosting cells are taken directly from patients’ tumors, grown outside the body, and then infused back into the body. The technology has been tried in various tumor types in the past, but it hasn’t generated a strong enough immune response. Immune-boosting drugs called cytokines can be injected along with the treatments, but because those drugs stimulate every T cell, they can cause harmful inflammatory side effects.

So the MIT researchers developed nanoparticles that can carry cytokines but that don’t release the drugs until the tumor-specific T cells hit their intended target. The particles consist of a gel made from the cytokine Il-15. A chemical change in the surface of T cells acts as a signal of sorts, prompting the nanoparticle to degrade and release its payload when it reaches the tumor.

“That allowed us to link T cell activation to the drug release rate,” said Darrell Irvine, Ph.D., a professor of biological engineering and of materials science and engineering, in the statement. “The drug is most efficiently being released at the sites where you want it and not in some healthy tissue where it might cause trouble.”

In 60% of mice whose T cells were engineered to express a target of melanoma, the nanoparticle-armed cells caused the tumors to disappear completely, Irvine and his colleagues reported in the journal Nature Biotechnology. They also discovered that the nanoparticles allowed them to give the mice eight times as much IL-15 than they could if they injected the drug directly into the body. Irvine was the senior author of the paper and a co-founder of Torque.

Torque was founded in Boston last year after raising a $21 million A round. Its founding management team is stocked with biopharma veterans, including chief medical officer Becker Hewes, M.D., formerly of Novartis, and CEO Bart Henderson, who previously founded Rhythm.

Deploying tumor-derived T cells against cancer is considered to be a promising, personalized approach to addressing solid tumors. One idea, being examined at the Ludwig Institute for Cancer Research in Switzerland, involves enriching “highly reactive” tumor-infiltrating lymphocytes (TILs) from ovarian tumors, for example. A University of North Carolina team is developing a CAR-T to treat the brain cancer glioblastoma that zeroes in on a surface protein called CSPG4, and Lion Biotechnologies is working on TIL technologies targeting sarcomas and pancreatic cancer.

MIT’s Irvine believes that any tumor type with a “known target”—meaning something the T cells can be programmed to recognize—could be enhanced with the cytokine-carrying nanoparticles. As Torque proceeds with clinical trials of the IL-15-infused cells in solid tumors, Irvine plans to study whether other cytokines may be even better at stimulating T cells to attack cancer.

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Malaria drug could make cancer treatments more effective

An existing malaria drug could improve the effectiveness of a new class of cancer therapies, called glutaminase inhibitors, if used in combination, researchers at Weill Cornell Medicine-Qatar (WCM-Q) discovered in a new study.

The research, published May 17 in Cancer Letters, analyzed the metabolic processes of cancer cells to show that the U.S. Food and Drug Administration-approved, quinine-based malaria drug Chloroquine could boost the effectiveness of the new glutaminase inhibiting drugs, which are currently being developed by global pharmaceutical companies. The findings could offer doctors and researchers a relatively simple way to improve outcomes for cancer patients who are prescribed glutaminase inhibitors.

Glutaminase inhibitors target a chemical process called glutaminolysis, in which the amino acid glutamine is broken down, releasing energy that cancer cells use to grow. Glutaminase inhibitors seek to disrupt this process, thereby depriving cancer cells of their energy source and slowing or stopping their growth. However, certain cancer cells can activate alternative ways to generate energy and thereby escape the drug’s action. This is where a new research approach called “rational metabolic engineering” comes in.

“We expose cancer cells grown in the laboratory to different doses of an anti-cancer drug and then measure the changes in almost all of the small molecules that are present in the cells, using a technique called metabolomics,” said lead author Dr. Anna Halama, a research associate in physiology and biophysics. “Using sophisticated computational methods, we then identify the molecules that the cancer cells are using to escape the drug’s actions, and conceive ways to block that escape route.”

In this first application of approach to glutaminase inhibitors, the researchers focused on two specific energy pathways that cancer cells use: lipid catabolism, which is the breakdown of fats, and autophagy, in which cells derive energy by degrading parts of their own structure. They found that both of these energy pathways were accelerated when the glutaminolysis pathway was suppressed with drugs, which allowed the cancer cells to survive.

“Since the anti-malaria drug Chloroquine is known to disrupt some of these energy-producing mechanisms,” Dr. Halama said, “our research prompted us to theorize that giving Chloroquine in combination with the glutaminase inhibiting drugs could lead to an improved suppression of tumor cells, which turned out to be the case.”

“The beauty of metabolomics profiling is that it lets us see how the cell’s metabolism behaves in different situations and with a very high level of detail,” said senior author Dr. Karsten Suhre, a professor of physiology and biophysics and director of the bioinformatics core at WCM-Q. “So with this method we can get very useful insights into the effects a drug has on the metabolism of tumor cells, helping us to understand how the disease works and to identify targets for potential new treatments.”

The findings may provide physician-scientists with a new strategy that can be replicated in other therapies. “The combined approach used in this study is uniquely relevant for future therapeutic strategies in cancer treatment and can be easily generalized to other drugs. The next important step is to test the efficacy of Chloroquine in combination with glutaminolysis inhibitors in a clinical trial.”

Dr. Khaled Machaca, associate dean for research at WCM-Q, said: “This type of research combining deep -omics phenotyping under specific pathological conditions identifies novel therapeutic interventions, in this case applied to cancer, that could be powerful in terms of disease interventions. The funding provided by QNRF for this type of research goes a long way toward both improving our basic knowledge base and generating potential therapeutic tools for Qatar and the world.”

More information: Anna Halama et al. Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis, Cancer Letters (2018). DOI: 10.1016/j.canlet.2018.05.017

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Majority of drivers don’t believe texting while driving is dangerous

People who text while driving are six times more likely to be involved in a car crash. To combat this problem, more and more states are adopting driving laws that require people to use hands-free devices in the car. Yet a new study shows that many drivers are still willing to take the risk, as ‘fear of missing out’ and separation anxiety keep them from abiding by the law. The study, published in Risk Analysis: An International Journal, reveals that many drivers don’t perceive texting and driving to be dangerous in certain driving scenarios.

In the U.S., mobile phone usage has been a factor in one quarter of all car collisions. However, actual crash risks vary based on the type of task being performed and the extent of its cognitive and physical demands on the driver. Talking on a mobile device increases crash risk by 2.2 times whereas texting increases risk by 6.1 times.

Observational studies have found that as many as 18 percent of drivers in high-income countries, and up to 31 percent in low- and middle-income countries, use their mobile devices while on the road, contributing to significantly reduced road safety. Despite laws prohibiting such behavior, mobile phone use while driving is expected to increase.

In the study, “Should I text or call here? A situation-based analysis of drivers’ perceived likelihood of engaging in mobile phone multitasking,” researchers found that drivers who are female, are frequent users of phones for texting/calling, have negative attitudes towards safety and are highly disinhibited report much stronger intentions of engaging in distracted driving. The research team included Oscar Oviedo-Trespalacios, Md. Mazharul Haque and Mark King from Australia Queensland University of Technology, and Simon Washington from the University of Queensland.

The researchers found that drivers engage in self-regulation when deciding whether to use their phones while driving, which is a process through which individuals develop strategies to cope with environmental factors while maintaining a high level of performance. For example, many drivers make use of stops to initiate using their mobile device, and many are able to restrain themselves to using phones only while stopped at intersections with signals. Many other researchers have also noted that drivers usually restrict engagement in heavy traffic or along curved sections of both urban and rural roads. This study sought to identify what factors contribute to self-regulation.

In the study, 447 drivers in South East Queensland, Australia, answered questions about perceived crash risk, perceived driving comfort, perceived driving difficulty, perceived driving ability, perceived likelihood of engaging in a voice call and perceived likelihood of engaging in texting.

The authors conclude that females are more likely than males to engage in mobile phone use while driving. More experienced drivers are less likely to engage in distracted driving. Results show that as the number of years with license increase, the probability of participating in distracted driving decreases, and drivers who are more disinhibited are more likely to drive distracted.

The researchers also found that drivers who hold the following beliefs are more likely to use a mobile device while driving: effects on driver are minor; I need a lot of convincing to believe it is dangerous; effects will last after the task is finished. Sixty-eight percent of participants reported needing a lot of convincing to believe in the dangers of texting and driving. However, demanding traffic conditions and the presence of law enforcement were reported as effective measures in reducing the likelihood of distracted driving. These results support high-visibility police enforcement programs as a means to combat distracted driving.

“Drivers are not good at identifying where it is safe to use their phone, it is safer for drivers to just pull over in an appropriate place to use their phone quickly and then resume their journey,” stated Oviedo-Trespalacios.

Drivers were much more likely to talk on their phones while driving than they were to use their phones to text. This is expected since the visual demands of texting compete directly with those of driving, whereas talking on the phone is mostly auditory.

The results from this study may contribute to more targeted distracted driving campaigns by highlighting opportunities for interventions. These campaigns should target safety attitudes to more effectively curb drivers’ motivations for engaging with their phones while driving. This study also confirmed the need to profile and target high-risk groups, particularly novice drivers and those who are overly attached to their phones, to develop messaging that considers their particular motivating factors.

More information: Oscar Oviedo-Trespalacios et al, Should I Text or Call Here? A Situation-Based Analysis of Drivers’ Perceived Likelihood of Engaging in Mobile Phone Multitasking, Risk Analysis (2018). DOI: 10.1111/risa.13119

https://bit.ly/2KSAHiS

IsoRay Gets FDA OK for Treatment of Recurrent Brain Cancers

IsoRay, Inc. (NYSE American: ISR), a medical technology company and innovator in seed brachytherapy and medical radioisotope applications for the treatment of prostate, brain, lung, head and neck and gynecological cancers and GT Medical Technologies, Inc., today announced the receipt of FDA 510(k) regulatory clearance for the brachytherapy technology, known as GammaTile™ Therapy that incorporates proprietary Cesium-131 seeds within customizable collagen-based carriers for the treatment of recurrent brain tumors.

IsoRay Medical, Inc., a wholly owned subsidiary of IsoRay, Inc., and GT Medical Technology had previously executed a collaborative development agreement and an exclusive ten-year supply agreement for GammaTile Therapy.  GammaTile leverages Cesium-131’s unique ability to deliver a highly targeted dose of intense radiation treatment while limiting radiation exposure to surrounding tissue.  The Centers for Medicare and Medicaid Services (CMS) has already clarified the coding for GammaTile in the hospital setting by assigning GammaTile Therapy to a new, specific ICD-10-PCS code.  Now that the FDA has issued regulatory clearance for GammaTile, the therapy can be made available in the near future to patients served by hospitals throughout the United States.

The new technology add-on (NTAP) program would qualify us for additional payments in the inpatient hospital setting under Medicare beyond what is currently available.  However, the date of the FDA clearance will not qualify for the current NTAP application cycle.  Therefore, GammaTile will need to re-submit for consideration under the NTAP program for fiscal year 2020, which begins on October 1, 2019.

“We are very excited that our partnership with IsoRay Medical has resulted in this new opportunity to provide an innovative solution for the hundreds of thousands of patients with recurrent brain tumors,” said Matthew E. Likens, President and CEO of GT Medical Technologies.  “As we worked to gain approval, GammaTile Therapy was implanted in over 100 patients in an IRB- approved study at the Barrow Neurological Institute in Phoenix, AZ.  We believe that experience will be a solid foundation for us to expand access to this important advancement in brain tumor therapy.”

“GammaTile Therapy utilizes Cesium-131 brachytherapy seeds to deliver a fast-acting therapeutic dose to the tumor bed,” said Lori Woods, Interim Chief Executive Officer of IsoRay, Inc. “The unique properties of Cesium-131 have started to revolutionize brain brachytherapy treatment, and GammaTile Therapy should help to accelerate the adoption of these procedures.  We look forward to working closely with GT Medical Technologies to support access to this critical treatment for patients with recurrent brain tumors.”

https://bit.ly/2J69BA0

Community Care Physician Network, UnitedHealth Join to Serve NC Medicaid

Community Care Physician Network LLC (CCPN) and UnitedHealthcare have established a new Advanced Care Medical Home and care management network relationship, giving North Carolina Medicaid beneficiaries access to CCPN’s 2,200 independent primary care providers in counties across the state under the new managed care system that will launch in 2019.

As a sign of the value they see in the relationship, UnitedHealthcare and CCPN will work closely together on innovative approaches to enhancing patient care and reducing health care costs.

“We’re excited to bring the benefits of CCPN’s high-performing primary care practices to UnitedHealthcare’s Medicaid beneficiaries with this new relationship,” said Steve Wegner, M.D., J.D., CEO of CCPN. “Our clinicians in counties across the state are ready to work hand-in-hand with UnitedHealthcare to enhance quality, patient experience, health outcomes and physician satisfaction.”

CCPN clinicians currently deliver health care services to 700,000 North Carolina Medicaid beneficiaries – more than 40 percent of people enrolled in Medicaid, the primary care case management program. These practices provide critical health care services in urban and rural counties across the state and care for a significant portion of North Carolinians with unique and complex health care needs.

“We are the first health plan to establish a definitive Advanced Care Medical Home relationship with CCPN because we believe our work together will lead to innovative approaches to meeting the needs of the people we serve across the state,” said Anita Bachmann, CEO of UnitedHealthcare Community Plan of North Carolina. “CCPN delivers high-quality health care and, most importantly, understands its patients, their unique health care needs and the communities it serves. We believe CCPN’s longstanding history of physician-driven and patient-focused care will complement UnitedHealthcare’s local and national experience and innovative programs.”

This new partnership provides the industry expertise, data and support that will enable CCPN to treat patients using an innovative value-based model focused on helping keep people healthy. UnitedHealthcare shares data with CCPN about patients’ underlying medical conditions, past treatments, missed care opportunities, medications prescribed and future care needs. This takes the burden off patients from having to connect information from each of their doctor’s visits themselves, and reduces duplicative tests and improves care coordination across specialties and care settings.

CCPN and UnitedHealthcare – which has served North Carolina for more than 20 years – collectively serve nearly 3 million people statewide.

https://bit.ly/2ufhde0

Bovie Medical in deal to sell core business

Bovie Medical Corp.’s stock BVX, +4.81% soared 10% toward a 20-month high in premarket trade Monday, after the medical device company said it reached a deal to sell its “core” business and the Bovie brand for $97 million in cash to Symmetry Surgical Inc. As part of the deal, which is expected to close in the third quarter of 2018, Bovie said it will enter into transition services, patent licensing, disposables supply and generator manufacturing and supply agreements with Symmetry. “This is a milestone moment for the Company, one that creates significant value for our shareholders by significantly enhancing our balance sheet with the addition of more than $70 million in estimated net cash proceeds after taxes and transaction related expenses and allowing us to further focus the organization on our strategic objective of commercializing our J-Plasma/Renuvion technology in the cosmetic surgery market,” said Chief Executive Charlie Goodwin. Separately, the company said it expects second-quarter revenue of $11.2 million to $11.5 million, above the FactSet consensus of $10.1 million. The stock has rocketed 92% year to date through Friday, while the S&P 500 SPX, +0.76% has gained 3.2%.

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Teva Launches Generic for Ulcerative Colitis in U.S.

Teva Pharmaceutical Industries Ltd., (NYSE: TEVA) today announced the launch of a generic version of Uceris®1 (budesonide) extended-release tablets, 9 mg, in the U.S.

Budesonide extended-release tablets are a glucocorticosteroid indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis.

“The launch of generic budesonide extended-release tablets signals an important addition to Teva’s portfolio,” said Brendan O’Grady, EVP and head of North America Commercial. “We continue to be focused on bringing affordable generic treatment options to our customers, including those living with chronic, life-long conditions like ulcerative colitis.”

With nearly 550 generic medicines available, Teva has the largest portfolio of FDA-approved generic products on the market and holds the leading position in first-to-file opportunities, with over 100 pending first-to-files in the U.S. Currently, one in seven generic prescriptions dispensed in the U.S. is filled with a Teva generic product.

Uceris® had annual sales of approximately $196 million in the U.S., according to IMS data as of May 2018.

https://bit.ly/2J8dap3