{"id":28443,"date":"2022-11-08T11:30:05","date_gmt":"2022-11-08T11:30:05","guid":{"rendered":"https:\/\/news.cancerresearchuk.org\/?p=24832"},"modified":"2024-11-03T15:13:13","modified_gmt":"2024-11-03T15:13:13","slug":"the-nobel-prize-winner-helping-us-treat-childrens-cancers","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/the-nobel-prize-winner-helping-us-treat-childrens-cancers\/","title":{"rendered":"The Nobel Prize winner helping us treat children\u2019s cancers"},"content":{"rendered":"
\"ProfessorProfessor Carolyn Bertozzi (right) with graduate student Mireille Kamariza<\/p>\n

” data-medium-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-300×168.jpg” data-large-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi.jpg”><\/p>\n

Professor Carolyn Bertozzi (right) with graduate student Mireille Kamariza<\/p>\n<\/div>\n

Professor Carolyn Bertozzi won the 2022 Nobel Prize in Chemistry for a technique she developed to look at tiny strands of sugar on the surface of our cells.<\/span> <\/span><\/p>\n

Well, that\u2019s one way of putting it. You could also say she took the kind of complex chemistry that used to require a sterile, high-tech science lab and modernised it for performance inside living organisms.<\/span> <\/span><\/p>\n

Bertozzi, who works at Stanford University in California, US, named her technique \u2018bio-orthogonal chemistry\u2019, which means it occurs in living cells, but doesn\u2019t interfere with other biological processes.<\/span><\/p>\n

In the years since she first developed it, Bertozzi\u2019s method, and the sugars she used it to look at, have helped advance our understanding of how cancer works. Now they\u2019re even giving us new ways to treat it.<\/span> <\/span><\/p>\n

Already, there are clinical trials testing whether bio-orthogonal chemistry could be used to aim chemotherapy drugs directly at tumours and minimise <\/span>side-effects<\/span><\/a> like nausea, exhaustion and hair loss. Other groups are using it to improve certain types of radiotherapy, and to make it easier to spot cancer cells in the body.<\/span> <\/span><\/p>\n

But Bertozzi herself is now focusing on <\/span>immunotherapies<\/span><\/a>, which help people\u2019s immune systems fight cancer. <\/span> <\/span><\/p>\n

And that\u2019s where we come in. As well as being a Nobel Laureate, Bertozzi is part of <\/span>NexTGen<\/span><\/a>, the <\/span>Cancer Grand Challenges<\/span><\/a> team we\u2019re co-funding it with the US National Cancer Institute and The Mark Foundation for Cancer Research to develop new ways to treat solid tumours in children.<\/span><\/p>\n

Bertozzi\u2019s role in the team comes back to those sugars. Cancers use them to protect themselves. NexTGen has a plan to stop that happening.<\/span> <\/span><\/p>\n

What we\u2019re missing<\/span> <\/span><\/h2>\n

Today, more than 8 in 10 children and young people (ages 0 to 24) in the UK survive cancer for 10 years or more. In the 1970s that number was more like <\/span>3 in 10<\/span><\/a>. <\/span> <\/span><\/p>\n

But there\u2019s one area where things haven\u2019t improved so quickly: solid tumours. Survival rates for children with some of these rare cancers have hardly changed in over 30 years.<\/span> <\/span><\/p>\n

We\u2019ve got much better at treating solid tumours in adults in that time, but cancers are different in children and young people. As well as appearing in different places for different reasons, they have far fewer mutations for us to target with advanced drugs, meaning more specialised treatments developed for adults aren\u2019t effective. <\/span> <\/span><\/p>\n

The Cancer Grand Challenges are all about taking a different approach to difficult problems. NexTGen isn\u2019t going to keep trying drugs just because they work for adults. Instead, the team is adapting a type of immunotherapy that works well on childhood blood cancers to target some of the unique features of solid tumours.<\/span> <\/span><\/p>\n

Cutting through the sugar coating<\/h2>\n

CAR-T cell therapy<\/span><\/a> has been used by the NHS to treat certain rare, high-risk blood cancers since 2018. It\u2019s given to an average of <\/span>15-30 children and young people<\/span><\/a> in the UK every year.<\/span><\/p>\n

It\u2019s a complicated and specialist treatment that involves immune cells being taken from the blood and altered to recognise cancer cells as a threat. When they\u2019re put back, these cells guide the immune system to attack cancers that it couldn\u2019t even see before.<\/span> <\/span><\/p>\n

CAR-T cells are tuned to target cancer cells.<\/p>\n

” data-medium-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small.jpg” data-large-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small.jpg” class=”wp-image-24847 size-full” src=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small.jpg” alt=”A 3D illustration of a CAR-T cell approaching a cancer cell” width=”200″ height=”200″ srcset=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small.jpg 200w, https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small-150×150.jpg 150w, https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/T-cell-attacking-cancer-cell-illustration-small-96×96.jpg 96w” sizes=”(max-width: 200px) 100vw, 200px”><\/p>\n

CAR-T cells are tuned to target cancer cells. Design_Cells \/ Shutterstock.com <\/span><\/p>\n<\/div>\n

Cancer cells in solid tumours aren\u2019t the same as those in blood cancers, so CAR-T cells need different directions to be able to find them. <\/span> <\/span><\/p>\n

Unhelpfully, most of the signs we currently look for on solid tumour cells are also common on important healthy cells elsewhere in the body. That means CAR-T cells tuned to find them can cause severe side effects.<\/span> <\/span><\/p>\n

So, to tackle solid tumours, we need a new type of target. That\u2019s why NexTGen is so interested in sugars. Cancer cells are especially thick with ones called sialoglycans. <\/span> <\/span><\/p>\n

There\u2019s a good, if devious, reason for this: healthy cells use these sugars to signal to the immune system that they\u2019re on the same side. As far as cancer cells are concerned, that makes them the perfect disguise. <\/span> <\/span><\/p>\n

Almost. <\/span> <\/span><\/p>\n

Healthy cells, which don\u2019t have anything to hide, prune what Bertozzi has called a neat \u201cgarden\u201d of sialoglycans. But cancer cells are nervous. They overcompensate, coating themselves in a dense sugar \u201cjungle\u201d.<\/span> <\/span><\/p>\n

On the one hand, this means normal immune cells can\u2019t see the cancer for the sugar. On the other, it means cancer cells make sloppy mistakes. Just as jungles are more diverse than lawns, cancer cells also grow unusual, or \u2018aberrant\u2019, sialoglycans that rarely appear on other cells.<\/span> <\/span><\/p>\n

Those are all potential targets for CAR-T cells. <\/span> <\/span><\/p>\n

In fact, we\u2019ve already found one.<\/span> <\/span><\/p>\n

The next generation<\/span> <\/span><\/h2>\n

It\u2019s a sugar called GD2, and there\u2019s a lot of it on cells from multiple types of children\u2019s cancer. Drugs targeting it in children affected by high-risk <\/span>neuroblastoma<\/span><\/a>, a rare type of cancer that usually starts in developing nerve cells, have been <\/span>available on the NHS since 2018<\/span><\/a>. <\/span> <\/span><\/p>\n

Recent studies from the US show that <\/span>72% of children<\/span><\/a> with high-risk neuroblastoma who received these anti-GD2 drugs alongside chemotherapy and immune boosters were still alive 5 years later. The average 5-year survival rate for children in the US with high-risk neuroblastoma <\/span>is around 50%<\/span><\/a>.<\/span> <\/span><\/p>\n

That\u2019s something to build on. Multiple researchers on the NexTGen team have promising results from early studies showing CAR-T cells that lock on to GD2 could be even more effective while causing fewer side effects. <\/span> <\/span><\/p>\n

It\u2019s also likely there are more targets like GD2, but, until now, no one has tried to investigate all the sugars that appear on solid tumours in children. <\/span>Bertozzi\u2019s lab gives NexTGen the Nobel-winning expertise to change that.<\/span><\/p>\n

\u00a9 Nobel Prize Outreach. Ill. Niklas Elmehed. <\/p>\n

” data-image-caption data-medium-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration.jpg” data-large-file=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration.jpg” loading=”lazy” class=” size-full wp-image-24834″ src=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration.jpg” alt=”An illustration of Carolyn Bertozzi” width=”200″ height=”200″ srcset=”https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration.jpg 200w, https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration-150×150.jpg 150w, https:\/\/news.cancerresearchuk.org\/wp-content\/uploads\/2022\/11\/Carolyn-Bertozzi-Nobel-illustration-96×96.jpg 96w” sizes=”(max-width: 200px) 100vw, 200px”><\/p>\n

\u00a9 Nobel Prize Outreach. Ill. Niklas Elmehed. <\/span><\/p>\n<\/div>\n

That\u2019s especially important because cancer cells can adapt under pressure from the immune system to produce different sugars instead of GD2. To tackle hard-to-treat tumours, we need to be able to predict these counters. <\/span> <\/span><\/p>\n

Bertozzi helps there, too. She is also an expert in \u2018Siglecs\u2019, the receptors on immune cells that interact with sugars. Like bio-orthogonal chemistry, these can be used as tools to identify different sugars in the body. <\/span> <\/span><\/p>\n

But that\u2019s not all. Unlike the receptors used on current CAR-T cells, Siglecs can look for multiple targets at once. By exploiting this, NexTGen can target different types of sugar within the same tumour, making it harder for cancer cells to adapt and escape.<\/span> <\/span><\/p>\n

It\u2019s a big change from what cancers are used to. Usually, the jungle of sugars on tumour cells suppresses the immune system by interacting with Siglecs on immune cells. For adult cancers, though, Bertozzi\u2019s lab has already developed multiple drug candidates that use Siglecs of their own to stop this happening, flagging cancer cells to the immune system while disrupting their defence mechanisms. <\/span> <\/span><\/p>\n

Those treatments are a foundation for NexTGen to develop truly \u2018next generation\u2019 CAR-T cell therapies for children and young people. Not only will they be able to seek out solid tumour cells that are using sugars to hide from the immune system, they\u2019ll also make it harder for cancers to become resistant to treatment.<\/span> <\/span><\/p>\n

And, as impressive as all that might sound, it\u2019s only a fraction of NexTGen\u2019s overall project.<\/span> <\/span><\/p>\n

Rising to the challenge<\/span> <\/span><\/h2>\n

It\u2019s difficult to see how this sustained focus on rare childhood cancers could happen without Cancer Grand Challenges. By bringing together the world\u2019s leading experts \u2013 and ensuring they <\/span>work closely with people affected by cancer<\/span><\/a> \u2013 we believe we can tackle the most complicated and pressing problems.<\/span> <\/span><\/p>\n

\u201cThis is something that really is only possible through Cancer Grand Challenges,\u201d said Professor Charles Swanton, our chief clinician and a member of the Cancer Grand Challenges Scientific Committee, when NexTGen was selected for funding. \u201cBecause these are relatively low incidence tumours, [they aren\u2019t] traditionally targeted by the pharma industry.<\/span><\/p>\n

\u201cCAR-T cell therapies have had incredible success in the context of childhood leukaemia, but their progress in solid tumours has been relatively slow,\u201d continued Swanton. \u201cThis Cancer Grand Challenge is primed to really accelerate progress in this key area of unmet need in paediatric oncology.<\/span> <\/span><\/p>\n

\u201cWe\u2019ve got all the tools now; we know what to do.\u201d<\/span> <\/span><\/p>\n

It seems the Nobel Prize committee would agree. <\/span> <\/span><\/p>\n

\n

Click chemistry and bio-orthogonal chemistry<\/h3>\n

Bertozzi shared the 2022 Nobel Prize in Chemistry with two other scientists: Professor Morten Meldal and Professor K Barry Sharpless. Working independently, Meldal and Sharpless discovered the first example of what Sharpless called a \u2018click chemistry\u2019 reaction.<\/p>\n

Click chemistry is a way of quickly and efficiently linking molecules without having to mimic the specialised processes used in nature. It also minimises the unwanted by-products left behind by traditional reactions.<\/p>\n

Bio-orthogonal reactions work in a similar way. Bertozzi created the first one when she applied elements of click chemistry to her own studies, updating and modifying it to work in living cells without disrupting their normal chemistry.<\/p>\n<\/div>\n

More on this topic<\/h3>\n<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

CAR-T cells are tuned to target cancer cells. Design_Cells \/ Shutterstock.com Cancer cells in solid tumours aren\u2019t the same as those in blood cancers, so CAR-T cells need different directions to be able to find them. Unhelpfully, most of the signs we currently look for on solid tumour cells are also common on important healthy […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-28443","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28443","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=28443"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28443\/revisions"}],"predecessor-version":[{"id":43157,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28443\/revisions\/43157"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=28443"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=28443"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=28443"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}