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Needle in a hay stack
Jeroen Wissink
CEO Uneedle | Intradermic | therapeutic vaccine delivey | cancer immunology
excellent article
We have many millions of mature helper T cells with unique T cell receptors (TCRs) in our body. In case of a serious infection or onset cancer our life depends on just one of them. How the Immune System Actually Works from Philip Dettmer - Kurzgesagd helps us understand.
Unique T cells
This diversity of mature helper T cells is fantastic feature of our immune system, crucial for our body's ability to recognise and respond to diseases and fight the onset of cancer.
We have a cure for any virus, bacteria or mutated cell
So for any virus, bacteria or cancer cell we carry a few matching memory T cells with a corresponding TCR to their antigens. We have the cure in us. Incredible, but true. And this is not new; this part of the immune system has evolved over hundreds of millions of years with us. And not just in humans, it works for most creatures - eaten alive without the immune system - in a similar way.
Dendritic cells to find a single T cell
In case of a serious infection or a cluster of unwanted, mutated cells the dendritic cells - one of the most potent antigen presenting cells - must trigger the helper T cells. Dendritic cells sample unknown or unwanted cells and break them apart to present fragments as antigens on their surface via so called MHC-II molecules.
Target for these antigens presented are the helper T cells, and there are a few helper T cell - somewhere in the body - with the matching receptors (TCR) to the antigen. Dendritic cells must travel to find that specific matching T cell, which is floating somewhere in lymph, in a lymph node. Since there are only a few helper T cells for every unique TCR combination - among many millions of different TCR combinations - it may take a few days before the match is found and before the adaptive immune system kicks in. Relatively slow, but very effective.
A single T cell multiplies
It is considered it a bit of a miracle that the match is always be made. But it is, and this is one of the true beauties of the immune system.
Once found, this unique memory helper T cell is woken up and after some time - remember it has been asleep for years or decades - starts to clone from a single cell to many millions. The counterattack to eliminate the pathogens has begun.
Essentially it is math: the number of specific proteins we - humans and animals, but also the pathogens - can present in the form of an antigen on the surface is limited to a few millions and that seems to be unique enough to uniquely identify viruses, bacteria or cancer antigens as foreign, to be eliminated from the body.
Killer T cells and B cells
At this point the adaptive response becomes more diverse. Some initial helper T cells transform into transform into killer T cells that actually help attack, but most cells transform to do act
Morning
The title of the presentation is intriguing
"Clinical Update on the DC Targeting Melanoma Vaccine, SCIB1 and The Modi-1 Vaccine Targeting Citrullination"
“DC Targeting Melanoma Vaccine”
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting innate immune cells that regulate adaptive immunity, including against cancer. Therefore, understanding the precise activities of DCs in tumours and patients with cancer is important.
This is an excellent article in nature 24th of Feb
Dendritic cells as orchestrators of anticancer immunity and immunotherapy
https://www.nature.com/articles/s41571-024-00859-1
Key points
* Combining DC-based anticancer treatments with other (immuno)therapies has shown promise in preclinical studies; however, patient selection, treatment sequencing and immunomonitoring require optimization in clinical studies to identify the most synergistic combinations.
* The development of improved DC-based anticancer treatments, including agents targeting DCs in vivo and natural DC-based vaccines produced ex vivo, has the potential to improve patient outcomes and such treatments are generally safe.
This is from Inaco on other board , please cane someone post next link to conference?
From other side
a week away from the next conference
lets hope any update gets an RNS
have we heard about the proposed Doublet in renal ? that was about 10 weeks ago from interims
Modi-1 to be assessed in renal cell carcinoma in combination with double CPI therapy in the ModiFY study pending protocol amendment by the MHRA
Thanks EE. Forgive me
I have had a very busy morning. Only scanned it sorry
Nottingham university hiring 3 researchers for glycocell engineering
3 industrial partners ? Who could they be , think Cath Merry mentioned one . ? Think about the government contracts mentioned in a slide from
Sarah Danson . Investigator for both scope trial and Moditope. The ref to the 2 Australian melanoma experts and achievements of eradication of Glibastoma by conducting a trials on himself. Wonder what that could have been
https://m.youtube.com/watch?v=oae33WdkLx8&list=PLF1-XapOV1fePHKA-Yd3PMIHwlr82NY9V&index=3&pp=iAQB
I would encourage you all to watch
“The GlycoCell Engineering Biology Mission Hub, the GlycoWeb BBSRC sLOLA, the anti-glycan antibodies of Scancell Ltd and other glyco-connected work at University of Nottingham put us very much at the centre of of the glyco-revolution in life science, bio-medicines and diagnostics. Watch this space “
https://jobs.nottingham.ac.uk/vacancy.aspx?ref=MED2006
Johnathan van tam ( Nottingham university)adviser to Moderna
We know research collaboration exists between Biontech and Scancell to
We know Genmab are working with Genmab
All very interesting innovations
Good luck to one and all
LinkedIn post from
Cathy Merry of Nottingham university
Professor of Stem Cell Glycobiology, Faculty of Medicine & Health Science
People - The University of Nottingham
This is fantastic! Really excited by the plans built up by John Heap and the team. The GlycoCell Engineering Biology Mission Hub, the GlycoWeb BBSRC sLOLA, the anti-glycan antibodies of Scancell Ltd and other glyco-connected work at University of Nottingham put us very much at the centre of of the glyco-revolution in life science, bio-medicines and diagnostics. Watch this space..
The University of Nottingham will lead a national hub that will develop vaccines, diagnostics and therapeutics, benefiting millions of people worldwide, thanks to funding from UK Research and Innovation (UKRI).
The GlycoCell Engineering Biology Mission Hub will receive £12.3 million in funding as part of an overall investment of £100m from UKRI’s Technology Missions Fund and UKRI and BBSRC’s core budgets.
https://www.nottingham.ac.uk/news/glycocell-engineering-biology-mission-hub
Link to the Todays Times article behind a paywall
https://www.thetimes.co.uk/article/exodus-from-aim-leaves-chorus-of-questions-in-its-wake-93d0mrvjx
extracts from article that are relevant :
The problem of weak valuations is behind C4X’s decision to take the company private at a meeting on Monday. Clive Dix, 69, its chief executive and the former deputy chairman of the Covid-19 vaccine taskforce, said: “We believe we should be valued at least five times, if not ten times what we are and therefore raising money at ten times the value would be much simpler. I don’t think it’s to do with the quality of the companies and the science. I just think that the environment, it doesn’t work. There’s no liquidity.”
Redx, a cancer drug developer, are down by more than 90 per cent from their 2015 listing, despite establishing four “major” partnering deals over the past five years.
Gervais Williams, head of equities at Premier Miton Investors, a long-term proponent of smaller listed companies, said it was not surprising that some businesses were leaving Aim. “The UK is cheap, but small caps are disgustingly, absurdly cheap,” he said. “A lot of companies feel that they’re not getting value for all of the extra cost and hassle of meeting the reporting requirements of being on Aim.”
Nevertheless, he reckons a broad rally in UK-listed shares is coming, with the FTSE 100 index flirting with a record high. This, he believes, will result in a “positive virtuous spiral” that will boost smaller listed companies. “I’m more bullish now than I’ve been for 30 years.”
Xodus from Aim leaves chorus of questions in its wake
https://www.thetimes.co.uk/article/exodus-from-aim-leaves-chorus-of-questions-in-its-wake-93d0mrvjx
The problem of weak valuations is behind C4X’s decision to take the company private at a meeting on Monday. Clive Dix, 69, its chief executive and the former deputy chairman of the Covid-19 vaccine taskforce, said: “We believe we should be valued at least five times, if not ten times what we are and therefore raising money at ten times the value would be much simpler. I don’t think it’s to do with the quality of the companies and the science. I just think that the environment, it doesn’t work. There’s no liquidity.”
Redx, a cancer drug developer, are down by more than 90 per cent from their 2015 listing, despite establishing four “major” partnering deals over the past five years.
Gervais Williams, head of equities at Premier Miton Investors, a long-term proponent of smaller listed companies, said it was not surprising that some businesses were leaving Aim. “The UK is cheap, but small caps are disgustingly, absurdly cheap,” he said. “A lot of companies feel that they’re not getting value for all of the extra cost and hassle of meeting the reporting requirements of being on Aim.”
Nevertheless, he reckons a broad rally in UK-listed shares is coming, with the FTSE 100 index flirting with a record high. This, he believes, will result in a “positive virtuous spiral” that will boost smaller listed companies. “I’m more bullish now than I’ve been for 30 years.”
https://www.thetimes.co.uk/article/exodus-from-aim-leaves-chorus-of-questions-in-its-wake-93d0mrvjx
The problem of weak valuations is behind C4X’s decision to take the company private at a meeting on Monday. Clive Dix, 69, its chief executive and the former deputy chairman of the Covid-19 vaccine taskforce, said: “We believe we should be valued at least five times, if not ten times what we are and therefore raising money at ten times the value would be much simpler. I don’t think it’s to do with the quality of the companies and the science. I just think that the environment, it doesn’t work. There’s no liquidity.”
Redx, a cancer drug developer, are down by more than 90 per cent from their 2015 listing, despite establishing four “major” partnering deals over the past five years.
Gervais Williams, head of equities at Premier Miton Investors, a long-term proponent of smaller listed companies, said it was not surprising that some businesses were leaving Aim. “The UK is cheap, but small caps are disgustingly, absurdly cheap,” he said. “A lot of companies feel that they’re not getting value for all of the extra cost and hassle of meeting the reporting requirements of being on Aim.”
Nevertheless, he reckons a broad rally in UK-listed shares is coming, with the FTSE 100 index flirting with a record high. This, he believes, will result in a “positive virtuous spiral
I agree C11 in 2020 was indeed interesting especially Redmile were also early investors of BioNTech let’s hope magic rubs off in all directions for patients and share price
The collaboration agreement with BioNTech 2019
Scancell to collaborate with BioNTech
Scancell to collaborate with BioNTech to investigate T cell receptor based therapeutics for the treatment of cancer
Agreement expands potential therapeutic utility of Moditope® to adoptive T cell therapy
Scancell Holdings plc, (‘Scancell’ or the ‘Company’) the developer of novel immunotherapies for the treatment of cancer, is pleased to announce that it has entered into a research collaboration with BioNTech for the potential development of innovative, T cell receptor based therapeutics for the treatment of cancer. This research collaboration combines Scancell’s Moditope® immunotherapy platform and BioNTech’s platform technology for high-throughput cloning and characterisation of naturally selected T cell receptors.
Moditope® represents a completely new class of potent and selective immunotherapy agents which could have a profound effect on the way that cancer immunotherapies are developed. It acts by stimulating the production of CD4+ T cells using citrullinated tumour-associated peptide epitopes which overcome self-tolerance and destroy tumour cells. The technology overcomes the immune suppression induced by tumours themselves without the need for checkpoint blockade inhibitors, thereby allowing activated T cells to seek out and kill tumour cells that would otherwise be hidden from the immune system.
Under the terms of the agreement, Scancell and BioNTech will enter into an initial research collaboration to discover and characterise T cell receptors specific for citrullinated epitopes from vimentin and enolase. These epitopes form the basis of Scancell’s first Moditope® development candidate, Modi-1. Upon completion of these studies, BioNTech will have the exclusive option to enter into a licence agreement for the development of cell receptor based therapeutics that are specific to Modi-1 epitopes.
A reminder of the research agreement with BioNTech
https://www.scancell.co.uk/scancell-to-collaborate-with-biontech
TF
Thanks for your post .. I found this was posted by Scancell in their LinkedIn page . And has had 64 likes
I find it odd again mentioning Biontech ?
I also posted A video of prof Sarah Danson ( an author of the abstract ) from the focus melanoma conference . Sponsors by Scancell . Ther was a whole slide seditious The uk government investment / partnership with Biontech and Moderna ?
Wonder where the research collaboration with Scancell and BioNTech agreed in 2019 !
Seems odd BioNTech mentioned in Rns post LinkedIn page and presentation at Mellanoma conference .
I have cut and paste from Scancell LinkedIn page
ICYMI, Scancell Ltd CEO Lindy Durrant presented data at American Association for Cancer Research on its open-label Phase 2 SCOPE trial investigating its cancer vaccine, SCIB1 in advanced melanoma, as part of the #AACR ‘Cancer Vaccines: Ready for Prime Time?’ clinical trials symposium.
The session covered progress from a number of other innovative clinical stage cancer vaccines including follow up data from the BioNTech mRNA vaccine, which reported T cells could still be detected at the three-year follow-up point. This is highly encouraging for the cancer vaccine space, particularly as SCIB1 has demonstrated an 85% response rate among 13 first-line advanced melanoma patients.
🔎 Learn more about SCOPE: https://lnkd.in/eivcrTxX
#cancervaccine #melanoma #AACR24 #immunooncology #immunotherapy
#ICYMI, Scancell Ltd CEO Lindy Durrant presented data at American Association for Cancer Research on its open-label Phase 2 SCOPE trial investigating its cancer vaccine, SCIB1 in advanced melanoma, as part of the #AACR ‘Cancer Vaccines: Ready for Prime Time?’ clinical trials symposium.
The session covered progress from a number of other innovative clinical stage cancer vaccines including follow up data from the BioNTech mRNA vaccine, which reported T cells could still be detected at the three-year follow-up point. This is highly encouraging for the cancer vaccine space, particularly as SCIB1 has demonstrated an 85% response rate among 13 first-line advanced melanoma patients.
🔎 Learn more about SCOPE: https://lnkd.in/eivcrTxX
#cancervaccine #melanoma #AACR24 #immunooncology #immunotherapy
Https://m.youtube.com/watch?v=oae33WdkLx8&list=PLF1-XapOV1fePHKA-Yd3PMIHwlr82NY9V&index=3&pp=iAQB
Prof Sarah Danson was author of abstract
This year's Melanoma Patient Conference session videos are now LIVE! 📽
You can access all of this year's sessions here: https://buff.ly/3xAae3u
Once again thank you to all of those who made this year's event such a great success! We look forward to welcoming you again next year.
#melanoma #melanomapatientconference #patientconference #mpc2024
Oncology is the single largest market in the global biopharma industry, worth over $200B. Here's a look at the top 15 drugs in the space, and some insights behind the numbers:
1. Several top sellers are facing LOEs soon: Pfizer's Ibrance faces competition in 2027, while Merck's Keytruda and BMS's Opdivo face expirations in 2028.
2. 4 drugs gained over $1B each in addition sales compared to 2022:
Keytruda (up $4.1B) Darzalex (up $1.8B) Imfinzi (up $1.5B) and Verzenio (up $1.4B).
The biggest decliner was BMS's Revlimid, which saw sales drop by almost $4B from 2022.
3. It is notable just how much these drugs depend on the US market for revenue - for several of the top drugs (e.g., Darzalex, Opdivo, and Ibrance), US sales accounted for well over 50% of total revenue.
The next few years have a lot in store - major LOEs, new modalities like ADCs, and more favorable capital markets - all of which will continue to make oncology one of the most dynamic parts of biopharma.
Infographic showing the 15 biggest oncology drugs by revenue in 2023, along with logos of the companies that made each drug
I agree Bobbust that’s some cash burn 🔥
Yes EE and they issues a press release prior ( see below ) however is didn't make it on the list for a recent article covering cancer vaccines see below
Inoculating Hope: The Landscape of Cancer Vaccination
Apr 08, 2024 | Reading Time: 2 minutes
https://www.delveinsight.com/blog/cancer-vaccines-landscape
Apr 08, 2024 | Reading Time: 2 minutes
Cancer vaccines represent a novel approach in cancer treatment, leveraging the body’s immune system to identify and eradicate cancer cells. Unlike traditional vaccines that prevent infectious diseases, cancer vaccines aim to stimulate an immune response against specific proteins found on cancer cells, potentially preventing cancer recurrence and impeding tumor progression. Recent strides in personalized medicine have facilitated the development of tailored cancer vaccines, which target individual tumor characteristics, thereby enhancing efficacy while minimizing adverse effects. Despite some setbacks in the past, ongoing research in immunotherapy, including cancer vaccines, remains a focal point of interest at this year’s AACR conference.
Here is our entry on the list
Scancell SCIB1 Advanced unresectable melanoma SCOPE
(NCT04079166) II CT024 A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma: Efficacy and safety results from the open-label Phase 2 SCOPE Trial
Press release ahead of presentation 7th of April 2024
New Phase 1 Data from Memorial Sloan Kettering Cancer Center Shows an Investigational Cancer Vaccine May Elicit Lasting Immune Response in Patients with Pancreatic Cancer
https://www.mskcc.org/news-releases/new-phase-1-data-from-mskcc-shows-investigational-cancer-vaccine-may-elicit-lasting-immune-response-in-patients-with-pancreatic
This speaker was after Lindy Durrant
CT025 Personalized RNA neoantigen vaccines induce long-lived CD8+ T effector cells in pancreatic cancer. Vinod P. Balachandran, New York, NY
https://health.usnews.com/doctors/vinod-balachandran-118798
So many meetings rooms . Considering a lot will want to listen to the 15 minutes in the PRIME spot at the worlds most important conference
Ballroom Theater Classroom Banquet Reception
20 A 1,330 860 580 1,880
20 A–B 2,214 1,352 980 2,865
20 A–C 3,052 1,856 1,380 3,857
20 B–C 1,330 896 600 1,985
20 B–D 3,034 1,912 1,380 3,943
20 C–D 2,132 1,352 980 2,865
20 D 1,400 848 680 1,960
20 A–D 4,800 2,904 1,960 5,820