Member Info for inanaco

find one that gives you confidence in its science to delivery more than one product, or its results are so impressive so that a risk of a binary pass or failure is minimised ..

wishful thinking on the boards, it would mean a party is actually swapping out the drug for a placebo ... as the trial failed what is the incentive behind this action ? as its an instantly traceable intervention, i have not looked at the data or what the trial is about.

On the cancer research project you have to look at each of the cancers that Modi3 could target and the specialist tuning of a vaccine probably including the Vimentin peptides so take head and neck cancer Oral squamous cell carcinoma (OSCC) what do we find .... Oral squamous cell carcinoma (OSCC) is a common public health problem worldwide with poor prognosis, which is largely due to lymph node metastasis and recurrence. Identification of specific molecular markers of OSCC with lymph node metastasis would be very important for early and specific diagnosis. In this study, we screened for the potential prognosis markers via unbiased transcriptomic microarray analysis in paired two OSCC cell lines, a lymph node metastatic HN12 cell line and a low metastatic parental HN4 cell line. The results showed that vimentin, with 87-fold increase of expression, was on the top of all upregulated genes in metastatic HN12 cells compared to non-metastatic HN4 cells. Treatment of non-metastatic HN4 cells with TGF-β1 induced epithelial to mesenchymal transition (EMT), with increased vimentin expression as well as enhanced migration activity. Consistently, knockdown of vimentin via siRNA resulted in suppressed invasion and migration activities of HN12 cells, suggesting an essential role of vimentin in EMT-related functions of OSCC cells. Finally, immunohistochemical (IHC) staining analysis showed that high vimentin expression was strongly associated with high lymph node metastases (p < 0.05), and poor overall survival (p < 0.05) in OSCC patients. Thus, high vimentin expression is strongly associated with increased metastatic potential, and may serve as a prediction marker for poor prognosis in OSCC patients. which gives you .......... epithelial to mesenchymal transition (EMT) scancells Modi1 ... Scancell’s first target for Moditope® is vimentin – a major cytoskeletal protein found in mesenchymal cells. Many epithelial tumours switch from expression of cytokeratin to vimentin during metastasis in a process known as epithelial mesenchymal transition (EMT); this change in phenotype enables the cell to become mobile and metastasize to new locations in the body. Scancell has now selected two modified vimentin peptides in which the arginine residues have been substituted by citrulline to form the basis of its first Moditope® development candidate, Modi-1. The inclusion of additional modified peptides from other Moditope® target proteins into Modi-1 is currently under review. Animal studies have shown that the two vimentin peptides stimulate potent anti-tumour responses and leads to significant improvements in survival, suggesting that the Modi-1 product could have outstanding potential as a novel immunotherapy. Immune response studies with cells isolated from cancer patients have confirmed that T cell responses were stimulated by both modified vimentin peptides. https://www.ncbi.nlm.n

Firstly, and most importantly, I would like to say a huge thank you to my supervisors Prof. Lindy Durrant and Dr Judith Ramage for their continued support and guidance throughout my PhD. I will be forever grateful to Scancell Ltd for their help and support in many aspects of my project. A particular thanks goes to Dr Victoria Pudney for her assistance in almost every aspect of my in-vivo work and Dr Rachel Metheringham for opening my eyes to the world of molecular biology. A special thanks also goes to Dr Ian Spendlove and Rob Moss for their help with the in vivo studies. http://eprints.nottingham.ac.uk/12584/1/Amy.Popple.Thesis.pdf

what happens once the t cells lock on ... its been filmed !! Go to: Lessons Learned from Intravital Imaging Experiments using intravital 2-photon microscopy showed that in the steady state, a dendritic cell (DC) interacts with 500–5000 T cells per hour, which migrate within lymph nodes with a velocity of 10–12 μm per min, thereby scanning uncounted peptide/MHC complexes (25–27). Interestingly, CD4+ and CD8+ T cells employ different strategies of surveillance: The interaction times of CD4+ T cells with DCs depend on MHC class II (MHC-II) molecules while CD8+ T cells traverse a LN slower and regardless of self-peptide/MHC-I complexes. They scan 160–200 and 300 DCs per hour and, thus, stay in a lymph node approximately for half a day and a day, respectively (28). Considering natural precursor frequencies, it has been assessed that at least 85 antigen-presenting DCs per lymph node are necessary to initiate a CD4+ T cell response (29). When confronted with a DC presenting antigen, specific T cells stop migrating and stay in touch with an individual DC for around a day (30–33). Within this period, the T cells undergo changes classically summarized as “blasting”: They increase in size, double their protein contents, increase their total RNA contents 30-fold, induce the expression of around 1300 mRNAs, and change their metabolism before proliferation ensues 24 h later (34–40).The stable interaction with one DC can be preceded by a phase of transient interactions with several APCs, the length of which is inversely correlated with APC density and antigen dose (41). Interestingly, it has been shown that, for CD8+ T cells, the phase of stable pairing with one DC is not necessarily required for expansion of effector clones, while memory differentiation is affected. These findings indicated that the memory potential of CD8+ T cells can be programed within the first 24 h of priming (36). The data also supported the relevance of observations that T cells can “memorize” sequential sub-threshold interactions with different APCs and accumulate such signals over time, perhaps via AP1 or NFAT (42–46).

Point of all this is i am not saying i am right ... what i am trying to do is understand it by reasoning, in which case its not an argument but it induces a mutual learning curve. certain aspects of what boom posted is correct, but did he understand it to reason it, in that this clonal deletion stage is a form of allowing selective T cells to escape with random TCR that are more readily able to lock on to the scancell modified epitope which is why i described them as reactive. its such a difficult topic to study like i said every part of it, is a PHD level subject in its own right, so your trying to put a post together that comes from many small areas to create one big one ...

so up to that point you have a range of t cells that are very reactive to poorly reactive should read after that point

mathematically its the same principle ... look at the dna as a number code. so in the T cell development stage any t cell, that recognised a number similar to a human self cell number is deleted "over reactive" so you have now a range of t cells that have been filtered but only at one fixed point, which is do not attack Self so up to that point you have a range of t cells that are very reactive to poorly reactive all of these cells can engage the APC ... but through natural selection only the reactive can get access to the protein and see it as a threat so they bind so the peptides induces an immunogenic response from selective T cells so basically a second filter is been applied, APC is recruiting reactive and discarding non reactive as they will not bind

Has anybody understood the posts today ?

it gives value to the RNS 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. wonder if the market will value it ?

did you understand my posts today ?

yes, pink ... with diamond sparkling eyes to match l .... you know that look, Winners always wear it yes Lindy had to develope this specific mouse for moditope testing

what medicinal cannabis ? ONW .. many have been there

its Lindy's mouse , which is why lindy's research is linked on the page

https://www.taconic.com/transgenic-mouse-model/abb-knockouttransgenic-hla-dr4

they are non standard mice,

You have not quite understood how this works. if you make a statement you have to try and reason it, what made you write it in the first place, what gave you that inspiration . its not for me to correct you as that would then appear is I am right etc which inflames a debate. so i specifically asked you to explain and reason your post leaving you with the knowledge that the statement may have flaws, which you yourself can correct by further reading and understanding. which is what i did in my post to yesterday on keytruda's inter action with natural cd4/cd8 from the mono studies with PD1 which you never replied to ... now that was significant as it directly relates to risk and value in scancell. Yet you have left the readers of your post thinking high risk applies without any refinement at all. SCLPInanacoSun 13:58 It's promising, it's positive and it can only help with the change in sentiment towards cancer vaccines . However, it's a different vaccine from a different company against different antigens in a different cancer (and HPV at that) with just 8 patients responding Is it proof that there is no risk here? Of course it isn't. Is it proof of synergy between SCIB1 and Keytruda? No it's not. It's encouraging that human trials in other vaccines support the preclinical research carried out by Scancell but it's no more than that at this stage. so your making quite bold statements ..... but no research to back you up that indicates """it will not work" when i was actually posting as per the author on "Process" which was Not cancer/antigen specific so for it not to work can you show me no efficacy in PD1 mono therapy keytruda in melanoma and no efficacy in SCIB1 in melanoma because the two combined form a process which my original post highlighted. tough ask eh ! to prove Risk ...

yes but it would involve costs on scancell to develop, i think its more likely that research would be spun off because of its cost of time v reward compared to human treatments

so what your describing is a memory cell ......... """" A CD4 T cell with surface receptors corresponding to those peptides then binds to the APC. """ A lymphocyte is shown in the center of this picture 1. After the naive T cell (N) encounters an antigen it becomes activated and begins to proliferate (divide) into many clones or daughter cells. 2. Some of the T cell clones will differentiate into effector T cells (E) that will perform the function of that cell (e.g. produce cytokines in the case of helper T cells or invoke cell killing in the case of cytotoxic T cells). 3. Some of the cells will form memory T cells (M) that will survive in an inactive state in the host for a long period of time until they re-encounter the same antigen and reactivate. Memory T cells are a subset of infection- and cancer-fighting T cells (also known as a T lymphocyte) that have previously encountered and responded to their cognate antigen; thus, the term antigen-experienced T cell is often applied. Such T cells can recognize foreign invaders, such as bacteria or viruses, as well as cancer cells. Memory T cells have become "experienced" by having encountered antigen during a prior infection, encounter with cancer, or previous vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time the immune system responded to the pathogen that entered the body. This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens. now do you understand my reasoning ?

sunday 20.51 statement that i questioned """" A CD4 T cell with surface receptors corresponding to those peptides then binds to the APC. """ like i said "corresponding" does not make sense which is why i asked you to refine or reason it. we are not experts, so the only way to work through this is reasoning ... and the result is probably not far from the mark.