War on cancer: Duke spinout pursues revolutionary treatment using polio vaccine - WRAL Tech Wire

Posted: 10 Dec 2020 12:00 AM PST

DURHAM – A Duke University spinout has developed an immune-boosting technology using variations of the polio vaccine that does more than wipe out a targeted solid tumor.

"It clears the body of others as well, not just where it's injected," said Matt Stober, president and CEO of RTP-based Istari Oncology.

Istari's primary technology platform is the Polio Virus Sabin-Rhinovirus Poliovirus (PVSRIPO). The results from multiple trials and preclinical research streams indicate that PVSRIPO has the potential to treat a variety of solid tumors that were previously thought of as untreatable.

Although the company began by focusing on the deadly brain cancer glioblastoma multiform, a treatment in Phase II trials, it discovered it has the potential to address just about every solid tumor.

It is potentially so versatile because most of us have been vaccinated with the polio vaccine, and its effects last the rest of your life, Stober explains. So, injected into a solid tumor, it causes a vigorous immune system response to attack the cancer.

Side-effects from the long-used polio vaccine are minimal, and the technology has already shown safety and effectiveness in clinical trials.

One of the company's trials is testing the PVSRIPO treatment along with checkpoint inhibitors. Istari executive John Higgins said checkpoints are part of the cancer cell-cycle that block the immune system. "Checkpoint inhibitors take the brakes off so the immune system can attack the cancer."

A 60 Minutes Episode featured how polio vaccines fight cancer:

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A better quality of life

The Istari technology does not have the nasty side-effects of many current cancer treatments such as chemotherapy, surgery and radiation. "Along with eliminating the tumors, we want to make the treatment less impactful so patients have a better quality of life, that's our mission," Stober said.

He also points out that many tumors are treatment-resistant and others become so, which is not a problem with the PVSRIPO treatment. Stober chose to take the helm at the company rather than retire because he saw his father die of the brain cancer Istari's treatment might cure.

The company, founded five years ago, raised about $4 million in 2017 according to US Securities and Exchange filings. Much of its initial funding came from research grants. It is currently raising a B round in an undisclosed amount. Istari has 34 employees and is hiring. It expects to add another 15 to 20 employees.

The company may go the IPO route eventually, sources say.

Clinical Trials

Phase 1 treatment-resistant melanoma data was presented at SITC 2020, which found that, 67% of patients responded positively in both injected and non-injected tumors.
IND clearance for LUMINOS-102, a Phase 2 trial studying PVSRIPO alone and in combination with an anti-PD-1 inhibitors in treatment-resistant melanoma
The first patient was successfully dosed in LUMINOS-101, a combination Phase 2 trial, studying PVSRIPO with Keytruda in patients with rGBM

Can tetanus and diphtheria vaccines reduce COVID-19 severity? - Medical News Today

Posted: 20 Jun 2021 12:00 AM PDT

Healthcare worker with COVID-19 vaccine — A history of diphtheria and tetanus vaccination may partly explain why some people with COVID-19 do not require hospitalization. David Greedy/Getty Images

Tetanus and diphtheria vaccines may produce protective effects against COVID-19.
Preliminary data finds severe disease outcomes significantly reduced among people who have received vaccines.
Scientists say that the vaccines could be achieving this by priming the innate immune response to fight.

The way that COVID-19, the infectious respiratory disease caused by the SARS-CoV-2 virus, progresses is different for everyone.

Although some people experience no or only mild flu-like symptoms and emerge unscathed from the infection, some require hospitalization and intubation due to respiratory failure and varying levels of organ support. For other people, it is fatal.

Termed "interindividual variation," health experts have largely attributed these differences in disease progression and outcome to differences in immune function.

Older adults, men, those with preexisting chronic health conditions, and people from minoritized communities are more likely to have severe COVID-19 and die.

When it comes to matters of immunity, however, there is another factor that comes into play: vaccination history.

Vaccines are key elements that train the immune system to fight a variety of pathogens that cause people to fall ill. They also stimulate the "innate" immune response, which is the body's first line of defense against invaders.

This is the part that has spurred scientists to investigate whether or not previous vaccinations can provide protection against other diseases, including COVID-19.

The notion that old vaccines might help in the fight against COVID-19 has persisted in the scientific community since the early days of the pandemic.

So far, live attenuated vaccines — such as the measles, mumps, and rubella (MMR) vaccine and the bacillus Calmette-Guérin (BCG) vaccine against tuberculosis — have dominated research and discussions on the matter.

For BCG, for example, some research has suggested that the vaccine can "enhance the innate immune response to subsequent infections" and reduce respiratory tract infections.

Newer studies, however, have looked into inactivated vaccines — particularly the diphtheria, tetanus, and pertussis (DTP) vaccines — to see if previous inoculations translate into less severe manifestations of COVID-19.

A 2020 study investigated the bacterial vaccines DTP and meningitis B and deduced that children's likely protection against SARS-CoV-2 could be down to cross-reactivity prompted by these vaccinations.

Cross-reactivity is an important mechanism for heterologous immunity, which happens when one pathogen induces an immune response to an unrelated pathogen in the future.

Because immunity wanes over time, especially when people do not receive booster shots, the researchers concluded that this could explain why older adults have more susceptibility to COVID-19.

Despite diphtheria, tetanus, and pertussis being caused by bacteria and COVID-19 by a virus, multiple studies have demonstrated heterologous immunity.

A 2021 study in the journal Medical Hypotheses suggested that with the aid of artificial intelligence, tetanus vaccination may be contributing to the reduced severity of COVID-19.

In line with that hypothesis, a recent study — which has not yet undergone peer review — added to existing research and suggested that older adults who have received a diphtheria or tetanus vaccine booster within the past 10 years may have a lower risk of severe COVID-19.

The researchers chose the 10-year timeframe to account for the waning of vaccine-induced antibodies over time. It is also the interval during which experts recommend booster shots.

As part of the study, the researchers analyzed the immunization records and COVID-19 testing data of 103,049 participants, with an average age of 71.5 years, using the UK Biobank cohort.

The researchers took into account age, sex, underlying respiratory diseases, and socioeconomic status.

Participants who had received any of the DTP vaccinations during the past 10 years were, on average, younger and had a higher socioeconomic status than those who had not been vaccinated against these diseases within the same timeframe.

It is important to note that having a lower socioeconomic status, along with a wide range of social determinants of health that contribute to health inequity, may be linked with a higher risk of COVID-19 and worse outcomes, according to previous research.

The results of the UK Biobank analysis showed that those who had received either a tetanus or diphtheria booster were less likely to receive a positive SARS-CoV-2 test. However, more importantly, the researchers found a statistically significant link between the boosters and the likelihood of having severe COVID-19.

Those who had received a tetanus booster were half as likely to develop severe COVID-19, and those who had received a diphtheria booster were 54% less likely.

The researchers found "no significant differences in the likelihood to test positive or [have] a severe case" with the pertussis vaccine, and they noted the small sample size.

The report is available on the medical website medRxiv ahead of peer review.

In most countries around the world, people receive vaccinations against tetanus in childhood, along with diphtheria and pertussis or polio. Some countries employ lifelong immunization programs to repeat booster shots every 10 years, while for other countries, health experts only recommend top-ups when traveling abroad or after injury.

In the United States, the Centers for Disease Control and Prevention (CDC) continue to recommend booster vaccines every 10 years after 18 years of age. However, these are not mandatory.

Officials also recommend regular boosters for tetanus, diphtheria, and, in some cases, pertussis in many European countries, especially for older adults. However, in the United Kingdom, because nationwide and routine immunization against tetanus only began in 1961, those born before that date do not carry protective antibodies for tetanus nor diphtheria.

According to World Health Organization (WHO) data from 2019, African countries such as Congo, Cameroon, Angola, and Ethiopia — where dropout rates for immunization are considerably high for vaccines that need repeating — only around 60% or less of the population receive their third tetanus booster shots later in life.

In South America, particularly in countries such as Haiti, booster coverage falls under 80%.

Bar Iraq and Syria, DTP booster rates remain above 70% for most countries in the Eastern Mediterranean and Middle East.

Vaccination coverage also varies around Southeast Asia, with most achieving above 70% coverage for the third booster of the DTP vaccine. In addition, for matters of tourism, the National Travel Health Network and Centre of Vietnam and the WHO still recommend that backpackers and travelers receive a tetanus shot before their visit.

The immune system employs a complex set of protective mechanisms against various pathogens. When it comes to immunity to SARS-CoV-2, preexisting immunological memory to other viruses or bacteria may well give it a head start.

However, the authors of the study do acknowledge that their data cannot establish a causal link between vaccine boosters, in particular diphtheria and tetanus, and the severity of COVID-19 but instead suggest a strong correlation.

They attribute the effect of the booster shots to a degree of protection against severe symptoms by way of stimulating the immune system. The authors write:

"One possible mechanism for this would be that these vaccines instill cross-reactive immunity, i.e., that they ready the immune response for a SARS-CoV-2 infection, perhaps through protein sequence similarities between the pathogens."

However, "the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations," the authors conclude.

Speaking to Medical News Today, David Cutler, a family medicine physician at Providence Saint John's Health Center in Santa Monica, CA, said that the data were not surprising considering previous evidence that unrelated vaccines, such as the measles, combined MMR, and BCG vaccines, could provide protection against COVID-19.

"But it does raise more questions than it answers. … There are areas of uncertainty which could not be addressed [in the study]. Were all vaccines accounted for? Were other social factors which led to people getting vaccinated responsible for the more favorable COVID-19 outcomes? What is the nature of the immunity which may have produced better outcomes?"

Cutler noted that the notion that routine vaccines provided benefit against COVID-19 was nonetheless intriguing.

"The clinical implication is that the benefits of vaccines may be even greater than previously realized. This is a potent reminder to receive not only a COVID-19 vaccine as soon as possible, but other routine vaccines when they are due."

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