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another new word
Biolistics
https://www.researchgate.net/publication/330858936_Abstract_B122_Development_of_a_new_immunotherapy_treatment_for_glioblastoma_multiforme
Glioblastoma multiforme (GBM) is the most frequently occurring primary brain tumor; it is a debilitating disease that is associated with poor prognosis, short median patient survival and a limited response to current therapies. As a result, there is a dire need for novel therapeutic interventions that are curative, or at the very least extend patient survival. Immunotherapy is an attractive option for the treatment of GBM due to its high specificity and minimal systemic toxicity. Peripherally activated immune cells have been shown to efficiently penetrate the brain parenchyma and access intracranial tumors, overcoming the blood-brain barrier, which hinders many molecularly targeted therapies. Two antigens, TRP-2 and WT-1, were found to be significantly expressed in GBM tissue sections while being absent from the normal brain. Peptide sequences known to be immunogenic were chosen from both TRP-2 and WT-1 antigens. The DNA sequences corresponding to these peptide sequences were then inserted into the complementarity determining regions of a DNA plasmid encoding an antibody known as ImmunoBody®; this vaccine has been shown to generate a higher avidity response than both peptide and peptide-pulsed dendritic cell vaccinations. As a result of the highly promising preclinical results shown, the ImmunoBody® vaccination is currently being studied in a phase I/II clinical trial for melanoma. As a result the ImmunoBody® DNA vaccine has been selected as our method of vaccination. Syngeneic C57BL/6 mice and humanized C57BL/6 HHDII/DR1 mice were used to assess the TRP-2 and WT-1 directed ImmunoBody® vaccines. Mice were vaccinated biolistically with the ImmmunoBody® plasmid coated onto gold particles using a gene gun. An initial priming dose was given on day 0 followed by a boost on days 7 and 14. Mice were vaccinated with either a TRP-2-ImmunoBody®, a WT-1-ImmunoBody® or a combination of the two. The immune response generated was determined by ex vivo IFN-? ELISpot using splenocytes derived from the spleen of immunized animals. Results from these dual vaccination experiments reveal that it is possible to use both of these vaccines in tandem without losing the specificity towards each vaccine-containing peptide. High level of peptide-specific IFN-?-releasing cells were detected directly ex vivo and the ability of these IFN-?-releasing cells to recognize targeT-cells that naturally express the WT-1 and TRP-2 antigens is being investigated. The efficacy of TRP-2-ImmunoBody® with or without PD-1 at treating syngeneic orthotopic GL-261Luc2 tumors implanted in
C57BL/6 mice is also currently being assessed. The combination of the two vaccines will also be assessed in the humanized HHDII/DR1 mice using a humanized B16 cell line that has had murine Beta-2m knocked out and HHDII and HLA-DR1 knocked in. Anti-PD-1 checkpoint blocka
Chester, you took the words out of my mouth. Tremendous research from cc, and once again the high regard Lindy is held in shines through. Sometimes that regard seems to make a mockery of the value of the science being developed in Scancell by it"s M/Cap of just only £31m.
Can"t remember a week with so few trades, seems like we are just treading water in this range, but we started the week 6.4/6.5, and although the bid has been pretty much the same, still taking plenty of shares at 6.7p despite showing 6.4, but the ask has increased from 6.46 to 6/98, some 8% odd.
I must have seen four seasons today, torrential rain throughout the night, heavy snow, albeit just for an hour, hailstones and then brilliant sunshine and blue skies in the afternoon. Here"s to more blue!! GN
bit more here
https://www.ejcancer.com/article/S0959-8049(18)30058-3/abstract
Crumbs, the original 2016 project funded by the Headcase Cancer Trust was looking at adding HAGE to SCIB1 to target glioblastoma. Looks like the project has been extended to look at TRP2 and WT1 so I guess they must believe that this combination will perform better than HAGE/TRP2.
https://www.investegate.co.uk/scancell-hlds--sclp-/rns/development-of-immunobody--vaccine/201606020700109671Z/
Also we know some work by a student has been done on a HAGE immunoBody...
'Dr. McArdle is also working on a HAGE- and mutated NY-ESO1-derived peptide sequences for the treatment of Triple Negative Breast Cancer (TNBC). HAGE antigen has previously been shown to be a prognostic marker for breast cancer patients and a predictor of response to adjuvant chemotherapy (Abdel-Fatah, et al. 2014). In collaboration with Dr. Abdel-Fatah, HAGE was shown to be expressed in 47% of TNBC (Abdel-Fatah, et al. 2016). Dr. McArdle has recently set up a new collaboration with Dr. Sara Mangsbo at Upsala University (Sweden) where immune complexes will be used to deliver and stimulate strong immune responses against HAGE and NY-ESO1 sequences.'
Swedish connection again too lol
It is ... good find, agree .......... sorry i was getting my head around the science
From scancells point of view ... looks like another Como trial ..
using Immunobody
with CAF09 eliciting strong immune responses in both models, and ImmunoBody® eliciting potent immune responses in C57Bl/6 mice. Indeed, a higher proportion of CD8+ T-cells were able to release IFN? and TNFa, to proliferate (Ki67 expression) and to degranulate (CD107a and Granzyme B expression) after short incubation with MHC class-I peptide.
CC / Crumbs thanks for the links. Good stuff.
this part .......
""The PAP-114-128 epitope ""
relates to this
This sequence has now been granted patent in Europe and in the US. Preclinical works are ongoing to gather the necessary data for a phase-0/I clinical trial for the treatment of hormone resistant prostate cancer.
Dr. McArdle has identified a mutated Prostatic Acid Phosphatase, PAP, derived sequence, which, when injected with CAF09, a strong adjuvant (kind gift from Dr. Dennis Christensen, Serum Institute, Denmark), is capable of generating T-cells that produce high level of IFNg against vaccine-derived wild-type peptides using ex-vivo ELISPOT assay. This sequence has now been granted patent in Europe and in the US. Preclinical works are ongoing to gather the necessary data for a phase-0/I clinical trial for the treatment of hormone resistant prostate cancer.
the Pap is the immune response Crumbs not the vaccine ....
""Prostatic acid phosphatase (PAP) is a prostate-specific protein""
CAF09 and ImmunoBody® were superior to CpG in inducing PAP-specific immune responses,
Thank you Crumbs,
This is the Scancell board that I have enjoyed in the past. Fantastic finds where Scancells tendrils are quietly at work. Scancells depth of science collusion really is like the skins on an onion, you can keep peeling back the layers to more and more collaborations and amazing developments.
This is a very pivotal year and now that the FDA have finally approved Ichors Trigrid 2 we are only months away from SCIB 1 combo trial. When the Modi 1 trial also gets the nod that will also be a big day.
So much forward momentum can happen this year, I know it's been a long wait but this companys science starts to make the headlines because of positive data it will have been well worth waiting for.
Chester.
There is also the PAP vaccine targeting prostrate and work has been done on HAGE too I think the PAP one is heading towards the clinic however not sure if ImmunoBody will be finally used but certainly, it could be ...
'the capacities of different delivery systems (CpG adjuvant, CAF09 adjuvant and ImmunoBody® DNA vaccine) to generate PAP-specific immunity were compared.'
https://cancerimmunolres.aacrjournals.org/content/7/2_Supplement/B118
“Vaccines can trigger immune responses that protect us from diseases such as hepatitis, measles and tetanus, and such immunotherapies also offer an approach for the treatment of cancer, as they are relatively non-toxic and have the potential to protect against cancer recurrence.”
Headcase Cancer Trust's founder Colin Speirs’ wife, Becky, died from GBM in 2010. They met while studying at Nottingham Trent University.
Colin said: “We’re delighted that Headcase continues to fund this genuinely ground-breaking project with NTU and that I, personally, can put something back into the University.
He said: “It’s their radical out-of-the-box thinking that we love; it fits perfectly with Headcase’s strategy to find a cure for this currently incurable disease. We look forward to moving this work, together, into human trials. The future gets written today.”
There certainly is a lot going on behind the scenes.
Tweeters tweet it lol
https://twitter.com/ecancer/status/1232700666730164224?ref_src=twsrc%5Etfw%7Ctwcamp%5Eembeddedtimeline%7Ctwterm%5Eprofile%3AHeadcaseCancerT&ref_url=http%3A%2F%2Fwww.headcase.org.uk%2F
Great find, as ever cc
Again I would think the work done with CRUK in choosing nano delivery makes it easier to get ImmunoBodies into trial:
'SCIB2 uses novel nanobody formulation Scancell’s second ImmunoBody, SCIB2, uses a new lipid nanoparticle formulation. The forthcoming CRUK-funded Phase I/II study will employ this via a standard injection, rather than using electroporation. Preclinical studies suggest the nanoparticle formulation is at least comparable to, and could be better than, using electroporation. Successful delivery should ease future regulatory interactions and also help with patient recruitment.'
Yes I think a lot of work has quietly been going on with this vaccine it would be great to see it get into the clinic
From Steph McArdles NTU page:
'In addition, in collaboration with Scancell Ltd she is investigating the potential use of a combined TRP2 and WT1 vaccine for the treatment of Glioblastoma. Many of these antigens can also be used against other cancer, for example, HAGE and WT1 are also being investigated for the treatment of Leukaemia.'
https://www.ntu.ac.uk/staff-profiles/science-technology/stephanie-mcardle
The University website on 25/2/2020 said, The Headcase cancer Trust continues to fund a new vaccine approach into an aggressive brain cancer glioblastoma multiforme (GBM). They will be working alongside Queen Mary University of London and France’s Hôpital Saint Louis.
Professor Graham Pockley, Director of NTU’s John van Geest Cancer Research Centre, said: “It is an exciting period for those of us that are working hard to develop new approaches for turning a patient’s immune system against their tumour – so called immunotherapy. Although success has been seen in many areas, effective treatments for GBM remain elusive.
“Combining a vaccine approach which has already been tested in another setting with strategies for preventing the tumour switching off the immune attack and enabling activated immune cells to enter the brain and reach the tumour has great potential.”
The vaccine ‘delivery system’ utilised by the scientists will be Scancell’s ‘Immunobody®’ technology, a version of which has been successfully used to develop SCIB1.
https://www.ntu.ac.uk/about-us/news/news-articles/2020/02/scientists-developing-new-vaccine-approach-for-most-aggressive-brain-cancer