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So, we have the words "rapid" and "Ultimately" but no mention of timescales.

I would also imagine that the timescales seen in the mouse experiments should not be expected in the Clinical trial and will certainly vary for each individual.

The impression I get is that the bombarding of the tumour with interferon gamma results in the situation in which the tumour can no longer suppress inflammation and, at that point, the tumour has had it.

Hi miavoce

The following article may give us a clue:

https://www.scancell.co.uk/Data/Sites/1/media/publications/papers/autophagy-citrullination-and-cancer-2016.pdf

"Tumors upregulate autophagy in response to stresses such as nutrient deprivation, oxygen deprivation, redox stress and
DNA damage. However, as tumors evolve they acquire many anti-inflammatory mechanisms including the inhibition of
interferon release from antigen-presenting cells. Vaccination with citrullinated peptides leads to a rapid increase in the number of pro-inflammatory CD4C T cells targeting the tumor resulting in interferon release, which ultimately flips the tumor environment from anti- to pro-inflammatory and results in tumor clearance"

Rumour has it that a proactive interviewer has been arrested for stalking Lindy :-)

Of more interest are the technicals that Lindy announces :-)

Yes Konar. It was discussed at the time on this BB.
I would imagine that too many TCells with different TCRs all going after the same cancer cell may cause problems. The TCells are all trying to establish contact with their particular target and chaos ensues.
Very relevant research for Moditope though.

Yes, it could be added to Modi1.
However, Lindy did publish research that going after too many targets limits the effectiveness of the vaccine.

https://www.researchgate.net/publication/356063197_Citrullinated_Epitopes_Identified_on_Tumour_MHC_Class_II_by_Peptide_Elution_Stimulate_Both_Regulatory_and_Th1_Responses_and_Require_Careful_Selection_for_Optimal_Anti-Tumour_Responses

"Interestingly, both citMMP21 and citGRI peptides individually, stimulated strong anti-tumour responses that were significantly better than the combined vaccine. In line with the citGRI T cell avidity, it required high dose immunisation to induce an anti-tumour response. This suggests that as the peptides within the combined vaccine had similar binding affinities to MHC-II the combination vaccine may have resulted in lower presentation of each epitope and weak anti-tumour immunity. Conclusion We demonstrate that tumours present citrullinated peptides that can stimulate Th1 and regulatory responses and that competition likely exists between similar affinity peptides. Characterisation of responses from epitopes identified by peptide elution are necessary to optimise selection for tumour therapy."

That the RSI has made a new world record!

Not for me.
I'm going for a 2nd Glymab deal or a first Avidimab deal.
Partner for Covidity will be next year after Lindy has published the results

Berm
"It will be interesting to hear LD's comments on whether or not SNAPvax is also a potential option for Modi1 in the future or whether each Modi is likely to require a different adjuvant."

Well Lindy always wants the best for her babies.
Let's see what she has to say about it.

Hi Ruck
They did turn up, they just forgot what sport they were playing.
They are still top with an easy game against Blackburn to come which is always a very friendly affair.

"I would think that Lindy will give more details at the AGM."
Of course, that's if Lindy turns up to the AGM. She may be enjoying her enhanced lifestyle :-)

Phase 1 trial targeted for 2024.
What it appears to solve are the manufacturing problems associated with the hydrophobic nature of Modi2.
Modi1 had similar problems that took well over a year to solve.
As an adjuvant, it also may be superior to Amplivant. I would think that Lindy will give more details at the AGM.

https://www.avideatechnologies.com/snapvax/in-vivo/

From reading this, it sounds like snapvac helps with delivery to APCs.

"Small particle sizes for optimal lymph node APC uptake
Enhanced immune responses with SNAPvax are, in part, driven by improved pharmacokinetics and antigen presenting cell (APC) uptake. SNAPvax’s small size (20 nm, diameter) enables passive trafficking to lymph nodes to access key populations of APCs, particularly dendritic cells (DCs), that promote T cell immunity."

"Modular surface properties enable targeting of specific APC populations
SNAPvax enables a plug-and-play approach to evaluating how different characteristics, such as surface properties, impact uptake by different APC populations. Such studies have identified optimal surface properties for targeting APCs by different routes of vaccination."

Plus, when entry to the APC is acheived, it has other uses:

"Codelivered immunomodulator programs the type of immune response
The modularity of SNAPvax also allows for optimization of the codelivered immunomodulator to fine tune the immune response. Both SNAPvax cancer vaccine (CV) and SNAPvax tolerance vaccine (TV) have been optimized for the immunomodulator class, potency and number needed for the therapeutic application."

"Linkers optimized for efficient antigen processing and presentation
Antigens must be processed and presented on the surface of APCs within the context of MHC molecules to enable priming and/or expansion of T cells. The amphiphilic peptides underlying SNAPvax include degradable linkers that are recognized by proteases in APCs, thereby enabling rapid antigen processing for efficient presentation to T cells."

It definitely looks like it is replacing Amplivant.

Holding long and strong with emphasis on long :-)

I suppose it is the way **** sapiens is heading these days

Yes you can tug your forelock but a well respected scientific term is censored

One thing at a time I suppose, and Lindy needs to see Modi1 working first. However, she did say that she was excited about the prospect of combining modi1 and modi2. I guess many cancers exhibit both citrullination and ****citrullination.

That sounds great Ivy but please don't mention Sheffield United:-)

It will be interesting to see how the modi2 trial is designed. It cannot be that far away. There are the same problems as modi1 in that the peptides once combined with amplivant are hydrophobic. I guess this may be delaying the trial. It does seem to have been preclinical for a long time.

But good entertainment C7.