As of January 10, 2022, over 13 billion COVID-19 vaccine doses have been administered — including hundreds of millions of mRNA vaccines by companies like Pfizer/BioNTech and Moderna. Following the surge in mRNA vaccine research for COVID-19, researchers are now seeking to apply their experience to cancer vaccines. Recently, BioNTech announced a strategic partnership with the government of the United Kingdom to provide up to 10,000 patients with personalized mRNA cancer immunotherapies by 2030.

“Our goal is to accelerate the development of immunotherapies and vaccines using technologies we have been researching for over 20 years,” says Prof. Ugur Sahin, CEO and cofounder of BioNTech, in a press release.

“The collaboration will cover various cancer types and infectious diseases affecting collectively hundreds of millions of people worldwide. If successful, this collaboration has the potential to improve outcomes for patients and provide early access to our suite of cancer immunotherapies as well as to innovative vaccines against infectious diseases – in the U.K. and worldwide,” he adds.

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The team behind the Oxford–AstraZeneca COVID-19 vaccine have used the same techniques to create a vaccine that could potentially ‘revolutionise’ cancer treatment.The researchers have designed a two-dose cancer vaccine using the same viral vector technology used in the Oxford COVID vaccine to increase the levels of anti-tumour T cells and shrink tumours in mice. The vaccine targets specific structures, known as MAGE proteins, found on the surface of many cancers.

“We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours. MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types,” said Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford.

“This broadens the potential benefit of this approach to people with many different types of cancer. “Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.”

When combined with existing anti-PD-1 immunotherapy treatments, the vaccine showed a greater reduction in tumour size and improved the survival of the mice. Anti-PD-1 immunotherapy is a promising method of cancer treatment that works by ‘taking the brakes’ off anti-tumour T cells and inciting them to kill cancer cells. However, it has so far proven to be largely ineffective thanks in part to the low levels of T cells in the majority of cancer patients.

This is where the tech borrowed from the Oxford-AstraZeneca vaccine comes in – a two-dose treatment can help to boost the levels of cancer-fighting CD8+ T cells. “Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer,” said Prof Adrian Hill, Director of the Jenner Institute, University of Oxford.”

The team now plan to begin their first human clinical trial of the vaccine used in combination with anti-PD-1 immunotherapy in 80 patients with non-small cell lung cancer later this year as part of a collaboration between Vaccitech Oncology Limited (VOLT) and Cancer Research UK’s Centre for Drug Development. “This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results,” said Hill.

Source: https://www.ox.ac.uk/
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https://www.sciencefocus.com/

A personalized “cancer vaccine” may help keep a deadly form of skin cancer from growing for years, a small new study in humans suggests. Unlike vaccines that prevent infections, such as measles and influenza, cancer vaccines are a form of immunotherapy that take down cancer cells that already exist. The vaccines train immune cells, called T cells, to better recognize cancer and target it for destruction, while sparing healthy cells in the body. For example, the new experimental vaccine works by training T cells to spot specific proteins on melanoma cells, a type of skin cancer. In the study, scientists found that the T cells continue to “remember” these proteins for at least four years after the vaccination — and they even learn to recognize more melanoma-related proteins over time.

“The only way that could have happened is if there was actually killing of the tumor cells. And presumably it was the T cells induced by the vaccine that did that killing,” said study author Dr. Catherine Wu, a physician-scientist with the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. That’s because, once killed, tumor cells fall apart and spill their contents; T cells then swoop in to examine these remains and log that information away for future attacks, Wu said.

While the results are promising, the new study only included eight patients, and more trials need to be conducted to pin down exactly how effective the vaccine is, she added. But as of now, the limited data hint that the vaccine triggers a persistent immune response and can help keep cancer under control, especially when combined with other immunotherapies, the authors noted. The new study, published Jan. 21 in the journal Nature Medicine, included patients with advanced melanoma who had recently undergone surgery for the cancer. The researchers took samples of the patients’ removed tumors and used them to craft personalized vaccines for each of the eight participants.

Source: https://www.realclearscience.com/

Scientists at Thomas Jefferson University who are developing a cancer vaccine to prevent recurrences of gastric, pancreatic, esophageal, and colon cancers say they have added a component that would make the vaccine more effective. The change makes the vaccine less prone to being cleared by the immune system before it can generate immunity against the tumor components.

The preclinical studies pave the way for a Phase II clinical trial opening to patients this fall, according to Adam Snook, PhD, assistant professor in the department of pharmacology and experimental therapeutics and researcher at the NCI-Designated Sidney Kimmel Cancer Center (SKCC)—Jefferson Health.

“Our data show strong immune responses in mice that might otherwise clear the vaccine, and suggests this approach will be more effective in the human trials we are starting shortly,” he said. “Adenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines. 

“Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.

“Here, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) derived from the capsid of Ad5 and fiber of the rare adenovirus serotype 35 (Ad35) to induce immune responses to the tumor-associated antigen guanylyl cyclase C (GUCY2C).

“In the absence of pre-existing immunity to Ad5, GUCY2C-specific T-cell responses and antitumor efficacy induced by Ad5.F35 were comparable to Ad5 in a mouse model of metastatic colorectal cancer. Furthermore, like Ad5, Ad5.F35 vector expressing GUCY2C was safe and produced no toxicity in tissues with, or without, GUCY2C expression. Importantly, this chimeric vector resisted neutralization in Ad5-immunized mice and by sera collected from patients with colorectal cancer naturally exposed to Ad5.

“These data suggest that Ad5.F35-based vaccines targeting GUCY2C, or other tumor or pathogen antigens, may produce clinically relevant immune responses in more (≥90%) patients compared with Ad5-based vaccines (~50%).”