Member Info for crumbs

It must have happened :)

'We have two candidate antibodies in which we have shown a hundred-fold and ten-fold reduction in potency, respectively, introduced by the change from mouse IgG3 to human IgG1. These make ideal candidates to test which alterations in the human IgG1 re-introduce this lost potency. We believe that this work will result in a number of very exciting prospects. It will permit the use of antibodies against clinically useful targets that would otherwise have failed at the 'humanisation' stage; it will allow the use of lower doses of antibody, with a lower risk of side-effects; and it will increase the potency of currently available antibodies, increasing their clinical effectiveness. We therefore consider that the proposed project is an excellent use of resources with patient and economic benefits encompassing our antibodies and many other therapeutic antibodies. Technical Summary Mabs targeting tumours show variable efficacy and improving this is a key goal to this $billion industry. Glycolipids are excellent targets for mabs as they are over-expressed in tumours and are co-accessory molecules for key survival pathways. Blocking these pathways can lead to direct cell killing. Despite the attractiveness of the targets, there are very few mabs recognising glycolipids as they fail to provide T cell help and induce low affinity IgM responses. We have overcome this limitation and produced high functional affinity mouse IgG3 (mIgG3) mabs that show potent in vitro and in vivo anti-tumour responses. These mabs show proinflammatory direct tumour killing without the need for immune effector cells or complement and can reinitiate immune responses in the tumour microenvironment. mIgG3 has the unique ability to non-covalently multimerise on the cell surface through intermolecular cooperativity, resulting in increased functional affinity and enhanced tumour cell killing. This only occurs at high antigen density (tumour) thus reducing off target (normal) toxicity. We have chimerised the mouse mabs to human IgG1 (hIgG1) but they have lost direct cell killing and have reduced functional affinity as intermolecular cooperativity is not present in human IgGs. By crosslinking the chimeric mabs with anti-human Ig anti-serum or by changing one key amino acid residue we have shown that direct killing is directly related to functional affinity. The next stage in development of these novel mabs is to recapitulate the functional affinity of the mouse mabs by introducing intermolecular cooperativity in the chimeric constructs. No one has mapped the mIgG3 cooperativity and the key amino acids that differ between hIgG1 and mIgG3 are not patented giving us a unique position. This project will not only instigate the development of our series of anti-glycolipid mabs but could be used by other groups to improve the therapeutic index of any mab.'

Might be of help:

'we have observed that during the molecular procedures necessary to allow an antibody to be used in patients, they often lose a substantial fraction of their potency. We believe that we now have an explanation for why this might be occurring, and we are seeking the funding to make the changes necessary to avoid this loss of potency. Antibodies are typically produced by immunising mice with a target 'antigen'. Antibody-producing cells are isolated from responding mice and the cells immortalised. The antibodies being produced are then screened for reactivity and clinical applicability, and the genes encoding the antibodies are cloned. The areas of the antibody that are not responsible for the target specificity (the 'constant regions') are then replaced with their human equivalent, in a process referred to as the 'humanisation' of the antibody. This is essential to create a clinically useful reagent; if the majority of the mouse areas remain, an immune response can develop in patients that negates the effectiveness of the antibody. We have observed that after this 'humanisation' process, the antibodies bind less strongly to their target and that many of the clinically beneficial effects of the antibodies are lost. We believe that this reduced potency is due to the replacement of the original mouse 'subclass' of the antibody, called mouse IgG3, as we do not observe it when other mouse subclasses are involved. Previous investigators have suggested that mouse IgG3 antibodies might combine together once bound to their target, in a way that other antibody subclasses do not. This stabilises binding and amplifies the clinical potency of the antibody. Our proposal is to confirm the areas of mouse IgG3s that are having this effect, and to transfer these areas to human IgG1'

https://app.dimensions.ai/details/grant/grant.3957088

Yes TF ... the tying of academia and commercial is a thing and one we will see more of in this field....

'Prof. Sahin is a doctor of medicine, immunologist and cancer researcher. His key focus is translating groundbreaking novel scientific ideas into medical innovations that help individual patients, an interest that was originally prompted by his experiences as a trained physician. His made key contributions in various fields of cancer immunotherapy covering the discovery of tumor associated cancer antigens, development of novel monoclonal antibodies for treatment of solid human cancers and various classes of RNA based immunotherapies. His team has pioneered the concept of individualized cancer immunotherapies and in particular the development of mRNA-based vaccines that are tailored to each patient´s cancer mutation profile. Ugur Sahin is Professor at the University Medical Center, Johannes Gutenberg-University, founder and managing scientific director of TRON and co-founder and CEO of BioNTech.'

Busy guy but let's see what NASDAQ value his part-timer IP at huh

Of course it is highly insulting BS and I stand by it crass or not... where did any of scancells tech come from? where did most the staff come from where are the labs!!! .... Lindys commitment to Notts is nothing but good news for scancell she is working on scancell tech probably full time and more! Take recent bringing in of the Glycan MaBs and AvidiMaB and the key now scancell full-time staff member who was key to creating them... So no but I will just say IMHO I disagree that this is any reason why we are at 7p.... the others I can agree with ... there :)

Yes brought in just before the glycan MaBs and AvidiMab were... which is why the part-timer jibe at Lindy and her IP made by moljen is highly insulting BS... Sahin is still uni connected and not full-time BioNtech either....

A046 I think is ours too... the Glycan specialist

Ooh well-done boom! missed that one which to me .... means there are 4! abstracts :))
And yes that helps ivy lol

Yes and looks like team scancell science will be there in force...

I can spot 3 abstracts.... sadly they do not give titles but I'm betting at least one is moditope based another is Glycans... and last dunno

And some big scancell related names there too... Sahin check.... Mellman check.... Meleif check.... Wargo check... almost like project blueprint get together....

See how many scancell team science abstracts you can find :)

https://static1.squarespace.com/static/56dee71e555986fb3ae583e2/t/5d77c3408439c80ad6480c42/1568129858122/CICON+-+Abstract+list+session+A+and+B.pdf

Like scancell will be presenting abstracts at CICON19 in Paris later this month... A big event....

BioNtech IPO ... seems an investor has let them down... however more of interest to us is this snippet

'BioNTech is also looking to the IPO to help fund some of its collaborations and get more assets into the clinic. The early-stage assets expected to benefit from the funding include candidates based on BioNTech’s research into CAR-Ts, T-cell receptors and mRNA-encoded antibodies and cytokines.'

https://www.fiercebiotech.com/biotech/biontech-files-for-ipo-after-investor-reneges-88m-promise

Indeed boom...and we'll get to see what NASDAQ values them at.... anyways hopefully more will be extracted painfully from BOD on Thursday about where we may be at with the BioNtech collab:)

Surely any modi1 TCR deal hangs more on what happens in the pre clinical lab work than any IPO....BioNtech have done deals since that IPO intention was announced....the 270 million they raised last year was the pot to be used around techs like TCR..

I thought they were after bigger money still interesting to watch

Ooh

Hope you get to go then ratty and report back with those all-important lifestyle details

Is attending the AGM on Thursday?... We have been very fortunate that for the last few AGMs posters here have managed to make recordings of the event and I'm hoping someone will this time too :) But if not any feedback will be most welcome .... revealing of choice of biscuits is always insightful :)

Considering where are and plans...

'Planned Impact
Our research benefits patients, commerce and the public with an overall goal of improving health and quality of life. Our research will provide a novel therapy for a wide range of cancer patients that should improve quality of life and achieve long term cure from this debilitating disease. The impact of our research spans both economic impact and patient benefit.

Commercial and economic impact
Nottingham University Therapeutic Antibody centre (NUTAC) has been established to develop and licence monoclonal antibodies (mAbs). Professor Durrant has had success with this process through her spin out company Scancell Ltd using external investment. The current business model is that NUTAC would develop and licence new mAbs using University (£500k)/grant (£500k) income so that all future income flows to the University will enable development of further mAbs. We have produced four mouse mAbs which show selective in vitro and in vivo tumour killing. Chimerisation of those mAbs to human IgG1 mAbs coincided with a reduction in potency. The current grant is designed to confirm the key residues in the mouse mAbs that are required for this increased potency and to transfer it to the human mAbs. This will not only allow us to produce 3 novel human mAbs for licensing to the Biotechnology/Pharmaceutical industry but could form a platform to improve the efficacy of all human mAbs.The top two lead mAbs, FG27 and FG88, could potentially treat 214,500 and 421,500 patients per annum based upon the % of tumours that express the target antigen. These are patients who currently have failed all other therapies and die of their disease. If we assume market penetration of 50% and a treatment price of £10,000 per patient this is a potential market of £1-2 billion.

Patient Benefit
Our mAbs can be used in the treatment of a wide range of cancer patients. As they not only directly kill tumours but initiative immune responses they should confer similar survival benefits to the new checkpoinhibitors which are currently curing 20-50% of advanced melanoma patients. If our mAbs are used to treat over 300,000 patients per annum and a conservative 20% are cured this could result in saving over 60,000 lives per annum.'

If only :)

https://gtr.ukri.org/projects?ref=MR%2FM015564%2F1