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Vaccinia Proposed Cancer Treatment Study Abstract

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    Posted: March 03 2016 at 2:35pm
New Results

Establishing elements of a synthetic biology platform for Vaccinia virus production: BioBrickTM design, serum-free virus production and microcarrier-based cultivation of CV-1 cells.

Shuchang LiuLudmila RubanYaohe WangYuhong ZhouDarren N. Nicholas Nesbeth
doi: http://dx.doi.org/10.1101/042275
This article is a preprint and has not been peer-reviewed [what does this mean?].

Abstract

Vaccinia virus (VACV) is an established tool for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. As a step toward realising these benefits we analysed the Lister Vaccinia virus genome with respect to refactoring options and propose a VACV genome engineering BioBrickTM. We then used the CV-1 cell line to produce a conventional recombinant Lister strain VACV, VACVL-15 RFP in a serum-free process. CV-1 cells grown in 5% foetal bovine serum (FBS) Dulbecco's Modified Eagle Medium (DMEM) were adapted to growth in OptiPRO and VP-SFM brands of serum-free media. Specific growth rates of 0.047 h-1 and 0.044 h-1 were observed for cells adapted to OptiPRO and VP-SFM respectively, compared to 0.035 h-1 in 5% FBS DMEM. Cells adapted to OptiPRO and to 5% FBS DMEM achieved recovery ratios of over 96%, an indication of their robustness to cryopreservation. Cells adapted to VP-SFM showed a recovery ratio of 82%. VACV production in static culture, measured as plaque forming units (PFU) per propagator cell, was 75 PFU/cell for cells in 5% FBS DMEM. VP-SFM and OptiPRO adaptation increased VACV production to 150 PFU/cell and 350 PFU/cell respectively. Boosted PFU/cell from OptiPRO-adapted cells persisted when 5% FBS DMEM or OptiPRO medium was present during the infection step and when titre was measured using cells adapted to 5% FBS DMEM or OptiPRO medium. Finally, OptiPRO-adapted CV-1 cells were successfully cultivated using Cytodex-1 microcarriers to inform future scale up studies.




A quick explanation for the hopelessly lost - from one only partially confused:  A proposed treatment for cancer involving making a virus target and kill the cancerous cells.  This is proving doubly effective as it both targets the nasties directly and encourages the host's immune system to fight them too.

This article details new production methods which double/quadrouple the viral production in improved growing mediums and shows that they survive cryogenic storage.

Vaccinia = (a horse virus related to cowpox which was the first smallpox vaccine)
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Less than an hour after I posted that, The Times posted this:  http://www.thetimes.co.uk/tto/science/article4705309.ece  which is an article suggesting that immunotherapy could be the magic bullet we are all praying for.  Sorry all, I do not have a subscription so I cannot post the full article, but the gist is lovely!
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Technophobe Quote  Post ReplyReply Direct Link To This Post Posted: March 03 2016 at 3:25pm
Luckily someone at the Mail is posting the same story.....

A cancer cure in just one jab? British scientists say they have found the disease's 'Achilles heel' paving the way for 'revolutionary' new treatments.

British scientists today claimed to have found cancer's Achilles' heel

  • In future, patients could be given bespoke therapies that hunt out and destroy every single cancer cell, wherever it is in their body
  • The first people could be treated in as little as two years, scientists say
  • Charity: 'It could prove a revolutionary way to treat or even cure disease'

By FIONA MACRAE SCIENCE EDITOR FOR THE DAILY MAIL

PUBLISHED: 19:00, 3 March 2016 UPDATED: 23:15, 3 March 2016

Cancer’s Achilles’ heel has been pinpointed by British scientists, raising hopes of a revolution in treatment – and even a cure.

In future, patients could be given bespoke therapies that hunt out and destroy every single cancer cell, wherever it is in their body.

The first people could be treated in as little as two years and, eventually, everyone from those in the early stages of cancer, to those who are riddled with the disease could benefit.

A spokesman for Cancer Research UK, which funded the landmark study, said that if it lives up to its promise, ‘it could prove a revolutionary way to treat or even cure cancer’

Despite advances in medicine, cancer claims more than millions of lives worldwide each year - and even so-called ‘wonder drugs’ only give patients an extra few weeks of life, on average.

The study, led by experts from University College London, gets to the heart of why existing treatments are often of limited benefit.

Although we think of a tumour as being a lump of identical cells, it grows and mutates over time.

Existing drugs typically zero in on one type of cell and, if the cancer changes too much, a medicine that seemed to help will stop working.

And even if the drug seems to wipe out the cancer, some highly-mutated cells may still be lurking and the disease returns.

However, some hardy mutations are found on every single cancer cell in a tumour and the UCL researchers have found a way of identifying them.



They have also shown that some lung cancer patients have disease-fighting white blood cells that are a perfect match for these common mutations.

In future, these white blood cells could be removed from the patient, grown up in the lab and then put back into their body to kill their cancer.

In theory, they should wipe out every cell.

Another option is use the information on the mutations to create a vaccine – a drug that tells the immune system to fight the cancer.

This breakthrough offers the hope we might just be able to turn the tide against advanced cancer – something we desperately want for our patients
Study co-author, Professor Charles Swanton

The approach is likely to be particularly successful in lung and skin cancer. But it is hoped that people with other forms of the disease, including breast and prostate cancer will also benefit.

And while the treatment could be given at any stage of the disease, it is likely to be of particular use to whose cancer is so advanced that they have run out of options.

Study co-author, Professor Charles Swanton said: ‘It offers the hope we might just be able to turn the tide against advanced cancer – something we desperately want for our patients.’

Some immunotherapies, treatments that use the immune system and its white blood cells to beat cancer, are already available, and producing stunning results.

In some cases, people thought to have only a few months to live have been able to return to work and live normal lives once more.

However, despite their promise they don’t work for everyone.



Read more:.

Professor Swanton said: ‘We think this approach will be very important for the treatment of cancer.

'In a few years’ time, we will be using immunotherapy for cancer just as much as chemotherapy today.'

He cautioned that that the research is still at an early stage and so hasn’t been used to treat any patients.

But while the history of cancer research is littered with failures, he hopes this has finally identified an Achilles’ heel.

HOW THE TREATMENT WORKS  

This study gets to the heart of why existing treatments are often of limited benefit.

Although we think of a tumour as being a lump of identical cells, it grows and mutates over time.

Existing drugs typically zero in on one type of cell and, if the cancer changes too much, a medicine that seemed to help will stop working.

And even if the drug seems to wipe out the cancer, some highly-mutated cells may still be lurking and the disease returns.

However, some hardy mutations are found on every single cancer cell in a tumour and the UCL researchers have found a way of identifying them.

They have also shown that some lung cancer patients have disease-fighting white blood cells that are a perfect match for these common mutations.

In future, these white blood cells could be removed from the patient, grown up in the lab and then put back into their body to kill their cancer.

In theory, they should wipe out every cell. 

The professor said: ‘This is really fascinating and takes personalised medicine to its absolute limit, where each patient would have a unique, bespoke treatment.

‘I will be disappointed if we haven't treated a patient within two years.

‘Do we think it's going to work? I hope this is going to result in improvements in survival outcomes.

‘If this doesn't work I'll probably hang my up hat and do something else.’

Professor Swanton, whose work was part-funded by the medical research charity the Rosetrees Trust, acknowledged that the bespoke nature of the treatment will make it very expensive.

However, existing drugs are already costly.

New cancer medicines typically cost £70,000 but only extend life by just over two months.

In contrast, a therapy that wipes out a patient’s cancer would allow them to return to work and contribute to the economy again.

Professor Peter Johnson, Cancer Research UK's chief clinician, said: ‘This fascinating research gives us vital clues about how to specifically tailor treatment for a patient using their immune system.’

He added that the ‘very exciting piece of fundamental cancer science will impinge in a huge way on way we treat cancer in the future.’

Dr Alan Worsley, also of Cancer Research UK, said: ‘Thanks to the ingenuity of our cancer researchers we may have found the tools necessary to give immunotherapy the precision guidance that patients so desperately need.’

Dr Marco Gerlinger, an immunotherapy expert at the Institute of Cancer Research, London, said the work was ‘intriguing’ but at too early a stage to be sure it will help patients.

He added: ‘The new study adds to the evidence showing how the ability to change and evolve enables cancers to relentlessly get their way, and shows that finding ways to stop cancers from evolving is likely to be key to defeating cancer.’


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