Andrada Mining acquisition elevates the miner to emerging mid-tier status. Watch the video here.
South African B 1.351
In contrast to the antibody responses, the T cell responses did not seem to be impacted by
variations between the virus strains (Figure 6F). Splenocytes from mice immunised with
either the original Lineage A vaccine or the B.1.351 (Beta) vaccine were stimulated ex vivo
with RBD and N peptide pools derived from the original sequence. T cell responses specific
for RBD and N were detected with little difference between the response induced by the
different vaccine constructs. These results suggest that mutations in the B.1.351 (Beta)
variant have less impact on the T cell responses.
One of the most concerning variants of concern (VoC) currently in circulation is B.1.351
(Beta). Recent data have suggested that although the approved vaccines induce responses
that can provide some cross-reactivity with the B.1.1.7 (Alpha) variant, they are less effective
against the B.1.351 (Beta) and P.1 (Gamma) variants [37-39]. To address this, we
engineered a new construct encoding the RBD protein containing the mutations within the
B.1.351 (Beta) variant alongside N linked to modified Fc (iV1) (also known as SN17). Sera
from mice immunised with the original DNA vaccine construct, the B.1.351 (Beta) vaccine
construct or the construct expressing the whole S antigen from the original variant were
analysed for reactivity to the original Lineage A SARS-CoV-2 S1 protein as well S1 protein
incorporating the mutations seen in the B.1.351 (Beta) variant by ELISA. Substantial
antibody responses were observed to the protein variants up to 1 in 100,000 dilution (Figure
6B). As noted above, sera raised against the original Lineage A vaccine exhibited a
decrease in reactivity to the B.1.351 (Beta) variant S1 protein compared to the Lineage A S1
protein with the EC50 decreasing from 4664 to 2949. The responses induced by the B.1.351
(Beta) variant vaccine generated higher titres to the B.1.351 (Beta) variant S1 protein (EC50
of 3931) with lower titres against the original Lineage A S1 protein (EC50 of 2086). The
variant vaccines induced higher titres to both the original Lineage A S1 and B.1.351 (Beta)
S1 proteins compared to responses induced by the whole S DNA vaccine (EC50 of 1389 and
644 respectively). The sera were also assessed in a similar antibody binding assay on the
MesoScale Discovery platform that includes the whole spike and RBD proteins from original
Lineage A, B.1.351 (Beta), B.1.1.7 (Alpha) and P.1 (Gamma) variants (Supplementary
Figure 2) where the same pattern of responses was observed. Sera from immunised mice
showed similar reactivity to either the original Lineage A and B.1.1.7 (Alpha) variants or the
B.1.351 (Beta) and P.1 (Gamma) variants, as might be expected based on their RBD
mutations. Interestingly, the sera from mice vaccinated with the original Lineage A vaccine
and the B.1.351 (Beta) variant vaccine showed similar titres of antibodies recognising the
Lineage A N protein and a N protein vari
It looks promising Chelsea. I think Bermuda explained it well;
'The vaccine elicits strong pro-inflammatory CD4 Th1 and CD8 T-cell responses to both proteins, with these responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain'
- in other words enhancing Covidity with Avidmab significantly increased the potency of the vax.
'One peptide, conserved between SARS-CoV and SARS-CoV-2 [35], stimulated a
response in cells from immunised HLA-A2 transgenic mice (N 138–146), thereby highlighting the potential of these T cells to recognise other coronaviruses.'
(SARS-CoV being the original 2003 SARS)
'These data compare favourably with other studies in which the whole S protein or an RBD trimer have been used to produce vaccine candidates that generate potent neutralising antibodies'
Then the fact that Avidimab has given us results and extension in Patent life is fab.
It will be peer reviewed and hopefully funding or a deal to follow?
https://www.biorxiv.org/content/10.1101/2021.06.18.448932v1.full.pdf
no.
Bertrand Delsuc
@BertrandBio
·
2h
proteins T-cell biased vaccine.
Of note, the cellular response seems indeed better with a variant-specific formulation, but as seen with $MRNA, the interest of a variant-specific (1.351) formulation for the humoral response seems close to null (see yellow marks on last chart).
https://twitter.com/BertrandBio/status/1406889326915555331?s=20
A novel bivalent DNA vaccine encoding both spike protein receptor-binding domain and nucleocapsid protein of SARS-CoV-2 to elicit T cell and neutralising antibody responses that cross react with variants
View ORCID ProfileVictoria A Brentville, View ORCID ProfileMireille Vankemmelbeke, Rachael L Methingham, Peter Symonds, Katherine W Cook, View ORCID ProfileRichard A Urbanowicz, Theocharis Tsoleridis, Christopher M Coleman, Kin-Chow Chang, Anne Skinner, Elena Dubinina, Ian Daniels, Sabaria Shah, James E Dixon, A Graham Pockley, Sally E Adams, Samantha J Paston, Janet M Daly, Jonathan K Ball, Lindy G Durrant
doi: HTTPS://doi.org/10.1101/2021.06.18.448932
Abstract
The efficacy of vaccines targeting SARS-CoV-2 is becoming apparent now that the mRNA and adenovirus vector vaccines that have been approved for emergency use are showing promise. However, the longevity of the protective immune response and its efficacy against emerging variants remains to be determined. To improve longevity and future protection against variants, we have designed a DNA vaccine encoding both the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and its nucleocapsid (N) protein, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4 Th1 and CD8 T-cell responses to both proteins, with these responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain. We have shown that the vaccine also stimulates high titre antibody responses to RBD which efficiently neutralise in both a pseudotype and live virus neutralisation assay and show cross reactivity with S proteins from the emerging variants Alpha (B.1.1.7) and Beta (B.1.351). This DNA platform can be easily adapted to target variant RBD and N proteins and we show that a vaccine variant encoding the B.1.351 RBD sequence stimulates cross-reactive humoral and T-cell immunity. These data support the translation of this DNA vaccine platform into the clinic, thereby offering a particular advantage for targeting emerging SARS-CoV-2 variants.
Dr O'Bryan-Tear holds the title of M.D and is a Fellow of the Faculty of Pharmaceutical Medicine, a medical organisation with professionals from the three Royal Colleges of Physicians of the United Kingdom.
He was previously Vice President of Global Clinical R&D at GlaxoSmithKline Biologicals.
Around a decade ago he became Chief Medical Officer of a Norwegian biotech company - later bought for $2.9 billion - where he worked on the development of a radiopharmaceutical for prostate cancer.
Dr Robert Miller is a Managing Partner in Artemida Pharma, a drug development consultancy and has represented a number of companies providing strategic expertise, medical management and clinical development support for both small and large pharmaceutical and biotechnology companies during his 30-year career in the industry, particularly in the fields of oncology and immune-oncology and affiliate member of the American Society of Clinical Oncologists.
Absolutely Ray,
FG27 and FG88 alone 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.
Someone mentioned the other day that we had 5. I missed out FG 88. There are very few anti-glycan monoclonal antibodies (mAbs), as glycans usually induce low-affinity IgM responses.
https://www.intechopen.com/books/carbohydrate/monoclonal-antibodies-against-tumour-associated-carbohydrate-antigens
https://link.springer.com/article/10.1007/s11307-020-01522-8
1- e FG129-ADC/AvidiMabTM, an antibody-drug conjugate (‘ADC’) that internalises
to liposomes in order to release the therapeutic through diffusion into the target cancer cell. The ADC has been seen
to clear human tumours growing on xenographs in a nude mice in vivo study. A FG129 patent has been accepted for
grant in USA and was awarded earlier this year in Europe and published in Brazil
2- FG27 is a pure stand-alone AvidiMabTM antibody that is seen to ‘punch’ holes in cancer cells and is being initially progressed for treatment of gastric cancer.
3- FL134 CART binds to SCLC, a particularly aggressive condition with a poor prognosis;
progression of this lab-based research into clinic is expected, however, to await identification of a suitable external
collaborative partner.
4- FG2811, targets T-cells rather than tumour cells, in order to
stimulate improved T-cell responses in cancer patients, or to target patients with auto-immune disease to inhibit Tcell over-expression.
ImmunoBody®
? COVID vaccine
? New patent incorporating AvidimabTM
? Moditope®
? Modi-1: TNBC, ovarian, renal and head and neck cancer
? Modi-2: homocitrullination (potentially lung, breast, colorectal,
prostate and pancreatic)
? Modi-3: potential to treat tumour recurrence
? Monoclonal antibodies
? FG129-ADC/AvidimabTM
? FG27 AvidimabTM – gastric cancer
? FL134 CART- SCLC (small cell lung cancer)
? FG2811 T cell targetting mAb
? New platform AvidiMabTM developed to improve the avidity (potency) of any mAb and the direct killing ability of anti-glycan mAbs
? TCR
? Technology developed, 8/24 screened with no response possibly due to low avidity CD4 response in unimmunised donors to modified
antigens. This technology may need to wait for the clinical trial
Maybe an idea to really push our mAbs/ ADC into trials. Big money about for them!
A summary of current studies include FG129-ADC/AvidiMabTM, an antibody-drug conjugate (‘ADC’) that internalises to liposomes in order to release the therapeutic through diffusion into the target cancer cell. The ADC has been seen
to clear human tumours growing on xenographs in a nude mice in vivo study. A FG129 patent has been accepted for grant in USA and was awarded earlier this year in Europe and published in Brazil. Scancell is also in discussions with other developers to establish if AvidiMabTM supports the effectiveness of other ADCs
a Phase 1 clinical study in Japan and a Phase 1/2 clinical study in the United States.
Bristol Myers Squibb will pay $650 million U.S. dollars to Eisai including $200 million U.S. dollars as payment toward Eisai research and development expenses. Eisai is also entitled to receive up to $2.45 billion U.S. dollars in potential future development, regulatory, and commercial milestones.
https://investors.bms.com/iframes/press-releases/press-release-details/2021/Eisai-and-Bristol-Myers-Squibb-Enter-Into-Global-Strategic-Collaboration-for-Eisais-MORAb-202-Antibody-Drug-Conjugate/default.aspx
Senior Scientist, T-cell immunology – Oxford
There is further information on this role here https://www.scancell.co.uk/senior-scientist-t-cell-immunology-oxford
Closing date: July 2 2021
Scientist, T-cell immunology – Oxford
There is further information on this role here https://www.scancell.co.uk/scientist-t-cell-immunology-oxford
Closing date: July 2 2021
Technician – Oxford
There is further information on this role here https://www.scancell.co.uk/technician-oxford
Closing date: July 2 2021
HTTPS://www.immunology.org/joint-bsi-ncri-webinar-what-do-cancer-t-cells-see
Lindy Durrant | Professor Of Cancer Immunotherapy
University Of Nottingham
Festival of Biologics Basel 2021
9 - 11 November
HTTPS://www.terrapinn.com/conference/festival-of-biologics/index.stm
SCANCELL Retweeted
Oxford Science Park
@OxfordSciencePK
·
54m
Occupiers
@OxfordSciencePK
are hiring like crazy! Have a look here https://bit.ly/3lEXPBx for jobs from
@Enara_Bio
@scancellpharma
@cablefreeltd
@Vaccitechplc
#Sitryx and more
mRNA vaccine
CureVac says its vaccine showed only 47% efficacy against #covid19 in 40K-person trial, citing "unprecedented context of at least 13 variants circulating within the study population."
HTTPS://www.curevac.com/en/2021/06/16/curevac-provides-update-on-phase-2b-3-trial-of-first-generation-covid-19-vaccine-candidate-cvncov/
It would be nice to get an update on adjusted timelines from Scancell
Scancell is ideally positioned to progress its lead product, SCIB1, which has already initiated its Phase II clinical study in melanoma, aiming to enrol a total of 25 patients, while also completing the preparation of GMP supplies required for regulatory submission to initiate Modi-1’s planned UK Phase I/II clinical study in H1 2021.
TPI considers the resource now provided will be sufficient for it to generate meaningful clinical data that addresses unmet needs, including readouts (SCIB1 Phase 2 & Modi-1 Phase1/2 interim data) within the next 18 months, while providing a cash runway for anticipated programmes beyond 2023.
Importantly in this respect, the Board considers it will be able to capture additional value in a number of areas including, for example, its AvidiMab™ platform and TaG antibodies, before needing to conclude licensing deals. Adding to this is the
ability to apply rapid application of its ImmunoBody® platform to the development of a second generation COVID-19 vaccine,
Modi 1, (‘CTA’) is targeted before end-2020, with a view to start the planned clinical
study in the UK in H1 2021.
Based on these timelines, assuming dose escalation recruitment complete within six months, interim data might
be available during H2 2021 (probably including safety information and potentially also early efficacy indicators); a
more extensive interim trial result read out might then be seen during 2022.
https://www.turnerpope.com/wp-content/uploads/2020/12/Scancell_Holdings_plc_19_11_2020_FINAL_BGv3.pdf
Scancell management now considers it has the resources necessary to progress Modi-2 to clinic, potentially for
indications including lung, breast, colorectal, prostate and pancreatic cancer due to the broad expression of such
antigens. A further development, Modi-3, potentially in combination with Modi-1, is considered to offer opportunity
as a vaccine to treat post-surgical tumour recurrence.
Are there many still here from 2012?
You never know, if Modi has spectacular results it could rocket again. We can but dream ;-) !
https://www.fool.com/investing/international/2013/01/31/12-bagger-scancell-holdings-offers-positive-result.aspx
Sam Robson
(TMFDriveBy)
Jan 31, 2013 at 3:30PM
LONDON -- Scancell Holdings (LSE:SCLP) reported first-half figures today, and brought us news of "encouraging preliminary results from part 1 of the Phase 1/2 clinical trial" for its lead vaccine SCIB1.
The developer of therapeutic cancer vaccines said that initial signs show evidence that the vaccine is producing an immune response in cancer patients, which "may also be associated with clinical benefit."
In view of the positive results and minimal side effects seen with the 4mg dose, Scancell has received approval to evaluate an 8mg dose in an extra group of patients, in parallel with part 2 of the phase 1/2 trial.
The vaccines are based on Scancell's patented ImmunoBody platform, approved in Europe, Australia and now the United States.
Scancell's chairman commented:
The company has also announced the development of a new platform technology, Moditope™, which the directors believe could have a profound effect on the way that cancer vaccines are developed.
Moditope stimulates the production of killer CD4 T cells with powerful anti-tumour activity, with management saying: "CD4 responses to cancer associated antigens have been notoriously difficult to generate whether presented as peptides, proteins or DNA. Scancell has identified and patented a series of modified epitopes that overcome this limitation."
The shares dropped off by 1% to 39 pence this morning, following news that Scancell made a loss of 923,020 pounds compared to H1 2011's loss of 893,404 pounds, with the balance sheet dipping to 2.57 billion pounds at Oct. 31, 2012, from 3.53 billion pounds at as of April 30, 2012.
However, 2012 was the year that saw the emergence of Scancell as an investment prospect, soaring from a low near the beginning of the year of 4.75 pence to finish 2012 near a high of 60 pence -- over a 12-fold increase! With the shares having fallen back slightly to hover around 40 pence, further successful tests in 2013 could see another giant leap in the shares' value.