Scientists are utilising the same technology used in the creation of the Oxford-AstraZeneca COVID-19 jab to develop a vaccine to treat cancer.
Researchers at the University of Oxford and the Ludwig Institute for Cancer Research have designed a two-dose therapeutic cancer vaccine using Oxford’s viral vector vaccine technology. The cancer vaccine, which has already been tested in mouse tumour models, has been shown to increase the levels of anti-tumour T cells infiltrating the tumours and improve the efficacy of cancer immunotherapy.
The study has been published in the Journal for ImmunoTherapy of Cancer.
The process of cancer immunotherapy involves turning a patient’s own immune system against a tumour. PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of ‘off switch’ that helps to prevent the T cells from attacking other cells in the body. Anti-PD-1 immunotherapy works by taking the brakes off these anti-tumour T cells, enabling them to kill cancer cells. Although this therapy has proved hugely successful in some cancer patients, it is ineffective for most.
Researchers have sighted low levels of anti-tumour T cells in some patients as one of the reasons for the poor efficacy of anti-PD-1 cancer therapy. The vaccine technology behind the Oxford-AstraZeneca COVID-19 vaccine generates strong CD8+ T cell responses, which are required for good anti-tumour effects.
In this study, the researchers developed a two-dose therapeutic cancer vaccine with different prime and boost viral vectors, one of which is the same as the vector in the Oxford-AstraZeneca COVID-19 vaccine. To create a vaccine that specifically targets cancer cells, it was designed to target two MAGE-type proteins that are present on the surface of many types of cancer cells. Known as MAGE-A3 and NY-ESO-1, these two targets were previously validated by the Ludwig Institute.
Reduction in tumour size
When trialled in preclinical experiments using mouse tumour models, the vaccine increased the levels of tumour-infiltrating CD8+ T cells and enhanced the response to anti-PD-1 immunotherapy. The combined vaccine and anti-PD-1 treatment resulted in a greater reduction in tumour size and improved the survival of the mice compared to anti-PD-1 therapy alone.
Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford, Member of the Ludwig Institute for Cancer Research and Director of the de Duve Institute, Belgium, said: “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. 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.”
In the next step of this research, scientists will carry out a Phase 1/2a clinical trial of the cancer vaccine in combination with anti-PD-1 immunotherapy in 80 patients with non-small cell lung cancer. This trial is due to take place later this year as a collaboration between Vaccitech Oncology Limited (VOLT) and Cancer Research UK’s Centre for Drug Development.
Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and Director of the Jenner Institute, University of Oxford, said: “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.
“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.”
Tim Elliott, Kidani Professor of Immuno-oncology at the University of Oxford and co-Director of Oxford Cancer, said: “In Oxford, we are combining our fundamental scientific expertise in immunology and antigen discovery with translational research on vaccine platforms.
“By bringing these teams together, we can continue to address the significant challenge of broadening the positive impact of immunotherapy to benefit more patients.”
Moderna chief predicts existing COVID-19 vaccines will struggle with Omicron variant
(Asian News Hub) – The chief executive of Moderna has just predicted that existing COVID-19 vaccines will be much less effective at tackling Omicron than earlier variants of SARS-CoV-2 and warned it would take months before pharmaceutical companies can manufacture new variant-specific jabs at scale, FR reported.
Stéphane Bancel said the high number of Omicron mutations on the spike protein, which the virus uses to infect human cells, and the suspected potential rapid spread of the variant in South Africa, suggested the current crop of COVID-19 vaccines may need to be modified next year to beat Omicron.
“There is no world, I think, where [the effectiveness] is the same level, we had with Delta,” Bancel said.
He added: “I think it’s going to be a material drop. I just don’t know how much because we need to wait for the data. But all the scientists I’ve talked to . . . are like ‘this is not going to be good’.”
Omicron has 30+ mutations in spike protein region, may bypass vaccines: Dr Guelria AIIMS chief
Says efficacy of vaccines, including those in use in India, needs to be evaluated ‘critically’
(Asian News Hub) – The new Omicron variant of coronavirus has reportedly got over 30 mutations in the spike protein region giving it the potential to develop a immunoescape mechanism, and thus the efficacy of vaccines against it needs to be evaluated critically, PTI reported as saying by AIIMS chief Dr Randeep Guelria.
The presence of spike protein facilitates a virus’ entry into the host cell and is responsible for making it transmissible and causing infection.
“The new variant of coronavirus reportedly has got more than 30 mutations in the spike protein region and therefore has the potential of developing immunoescape mechanisms. As most vaccines (work by) forming antibodies against the spike protein, so many mutations at the spike protein region may lead to a decreased efficacy of COVID-19 vaccines,” AIIMS Director Dr Randeep Guelria told PTI.
In such a scenario, the efficacy of vaccines, including those in use in India, needs to be evaluated “critically”, he said.
The future course of action will depend on what more data on its transmissibility, virulence and immunoescpae shows, he said.
The Indian SARS-CoV-2 Genomic Consortia INSACOG is closely tracking the new variant of COVID-19 called B.1.1.529 and its presence has not been detected yet in the country, officials have said.
Dr Guleria emphasised the need to be very vigilant and having aggressive surveillance both for international travellers and in the region where there is a sudden increase in the number of cases.
“Also, we must ask everyone to religiously follow Coivd-appropriate behaviour and not let their guards down. Also, it has to be ensured that people get both the doses of vaccine and those who have not yet taken the jab are encouraged to come forward to take it,” he said.
The new, and potentially more contagious variant, was first reported to the World Health Organization (WHO) from South Africa on November 24. It has since been identified in Botswana, Belgium, Hong Kong and Israel among other countries.
On Friday, it was designated a ‘Variant of Concern’ by the WHO, which named it Omicron. A ‘Variant of Concern’ is the WHO’s top category of worrying Covid-19 strain.
The Centre on Thursday asked all states and union territories to conduct rigorous screening and testing of all international travellers coming from or transiting through South Africa, Hong Kong and Botswana.
In a letter to the additional chief secretary/principal secretary/secretary (Health) of all states and union territories, Union Health Secretary Rajesh Bhushan asked them to ensure that samples of travellers turning positive are sent to the designated genome sequencing laboratories promptly.
As new Covid variant surfaces, Doctors body calls for enhanced genome sequencing
(Asian News Hub) – With the emergence of a new Covid-19 variant carrying worrisome mutations, Doctors Association Kashmir (DAK) on Saturday called for enhanced genome sequencing of Covid-19 positive samples to look for the variant in the valley.
“We need to expedite the genome sequencing to identify the variant early and protect the community from another wave of Covid-19,” said DAK President and Influenza expert Dr Nisar ul Hassan.
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“Picking up the variant early is key to formulate appropriate and effective health policy that would help prevent and control its spread in the community,” he said.
The DAK President said genome sequencing is a laboratory method that is used to identify changes (mutations) in the genetic structure of the virus.
“A new variant of Covid-19 B.1.1.529 has surfaced in South Africa and has also been identified in Botswana, Belgium, Hong Kong and Israel,” he said.
Dr Hassan said the variant has 32 mutations in the region of the genome that controls production of the viral spike protein.
“The spike protein of the virus is critical for viral binding and entry to human cells. It is also the chief target of antibodies that the immune system produces to fight Covid-19 infection.” he added.
“Dubbed as Omicron, WHO has designated the new variant as variant of Concern,” said Dr Nisar.
He said a variant is labeled as variant of concern when the evidence shows the virus is more infectious, is causing more severe disease and is less responsive to existing control measures such as diagnostics, vaccine or treatment or a combination of these factors.
“South Africa has reported a fourfold increase in the number of new cases coinciding with the emergence of the new variant.
Many countries including Europe, US and Canada has imposed travel restrictions from South Africa and several other African countries,” he added.
Spokesperson DAK Dr Riyaz Amad Dagga said in today’s connected world, an outbreak anywhere is a risk everywhere.
Kashmir being the most favorite tourist destination, the mutant can come to us anytime. We have to be prepared and alert.
“We have to prepare in advance,” he said adding advance planning and preparedness is critical to help mitigate the impact of any eventuality.
General Secretary DAK Dr Arshad Ali said the best way to prevent the variant is to stop it from coming in as once the virus enters the community it is difficult to control it.
“Passengers at Srinagar international airport especially coming from affected countries should be rigorously screened to prevent the entry and spread of the variant in the valley,” he said.
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Moderna chief predicts existing COVID-19 vaccines will struggle with Omicron variant
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