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That’s funny. My post was merely full of quotes from MHRA. It appears you did not need to read between the lines.
The Durham Bulls moved up to MLB?
Please, go on believing acceptance and review has not started.
Meanwhile:
MHRA February 12, 2024
Therefore, we are now in a position to confirm that an MAA is held for DC-Vax-L.
We understand that this market authorisation application applies for this product to be used in a serious condition that is often associated with poor prognosis. However, the benefits and risks still need to be carefully weighed and considered. Please be assured that our assessment teams will endeavour to complete their reviews and assessments as soon as is reasonably possible without compromising on safety considerations.
….Our explicit commitment to ‘risk-proportionate regulation’ also represents a significant intent to increase regulatory oversight on high-risk medical products, applications and indications, especially in relation to new technologies, with a parallel reduction in regulatory oversight on products where there is clear evidence of a lower risk to patients.
Think of it this way.
If one is healthy, but they are given one of the following:
Chemotherapy, Car-T, Checkpoint inhibitors, antibody drug conjugate or Tumor treating fields,
Safety and diminished quality of life would be a major/constant concern.
No clue.
Thermos seems to imply a whale like himself might be on an nda. If there are many whales on NDAs, I’d suggest they are waiting for a particular event. If that unspecified event becomes reality, I’d suggest things will happen very fast. Then again, maybe Thermos is fos. You choose.
🔑Sure, but then they directed Stonk to the 2023/2024 business plan. Which appears to give us a very good idea of what labels they are using to carry out swift approval decisions in priority areas.
”2.1 Deliver predictable and reliable operational performance having defined our priority improvements for our core services to ensure swift and robust decisions on medical products, safety signals and compliance.
Identify service improvements across all priority areas with robust plans for implementation and effective change management to be in place by end Q4 [2023]
Eliminate current service backlogs by end of Q4 [2023] keeping stakeholders up-to-date.
Deliver phase one of our innovation-enabling and risk-proportionate medicines compliance strategy including the development of a pilot project for an outcome-based model by end Q4 [2023]
….Our explicit commitment to ‘risk-proportionate regulation’ also represents a significant intent to increase regulatory oversight on high-risk medical products, applications and indications, especially in relation to new technologies, with a parallel reduction in regulatory oversight on products where there is clear evidence of a lower risk to patients.
Here was the related phase I trial to the current phase ii preprint trial.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071163/
Again, cosponsor of Phase I was NWBO.
https://classic.clinicaltrials.gov/ct2/show/NCT01204684
Phase ii trial.
Primary completion date January 31, 2024.
The phase I was sponsored by NWBO.
Autologous DC was/is DCVax-l
https://classic.clinicaltrials.gov/ct2/show/NCT01204684
Phase ii trial.
Primary completion date January 31, 2024.
The phase I was sponsored by NWBO.
Autologous DC was/is DCVax-l.
🔑MHRA 2023/2024 business plan.
….Our explicit commitment to ‘risk-proportionate regulation’ also represents a significant intent to increase regulatory oversight on high-risk medical products, applications and indications, especially in relation to new technologies, with a parallel reduction in regulatory oversight on products where there is clear evidence of a lower risk to patients.
🔑From MHRA’s 2023/2024 business plan last updated September 2023.
”2.1 Deliver predictable and reliable operational performance having defined our priority improvements for our core services to ensure swift and robust decisions on medical products, safety signals and compliance.
Identify service improvements across all priority areas with robust plans for implementation and effective change management to be in place by end Q4 [2023]
Eliminate current service backlogs by end of Q4 [2023] keeping stakeholders up-to-date.
Deliver phase one of our innovation-enabling and risk-proportionate medicines compliance strategy including the development of a pilot project for an outcome-based model by end Q4 [2023]
Fully embed our new SafetyConnect vigilance system and realise patient and operational benefits by end Q4.”
I see you don’t understand the difference between cancer and virus treatment. Even the mRNA companies themselves state cancer is far more complex and challenging to treat than a virus that is foreign to the body.
Twerkingcurd, uncertain distant mRNA therapy for cancer involves unecessary and hope based steps, does not use all relevant antigens, repeats failed concept of human selected antigens and is essentially a boondoggle. Still, best of luck to them. Oh, that’s right, you liked Argos.
Tell the chancellor.
“This will allow, from 2024, the MHRA to introduce new, swift approvals systems, speeding up access to…. ground-breaking technologies such as cancer vaccines and AI therapeutics for mental health.” Source: Chancellor unveils a Budget for growth - GOV.UK (www.gov.uk)”
Glad to see you received a response.
Even after intending to wipe out all B-cells and B-Cell tumor cells with Car-T:
Although CD19 CAR-T cell therapy has achieved amazing overall CR rates in patients with R/R B-ALL and B-cell lymphoma (Larson and Maus, 2021), 40%–60% of CR patients eventually experience relapse.
As always, an interesting article by DD. Two topics, I believe DD might need to research more on are data exclusivity and biologic exclusivity.
While Flaskworks protects the manufacturing process, biologic exclusivity protects the end product.
Let’s pretend some hacks, let’s say their initials are LC and EX, want to make a biosimilar of an ATMP cell therapy like DCVax-l.
1. Could they just try to copy it and get a marketing license?
Answer: Not for about a decade after approval due to biosimilar restrictions
2. Could they just use a similar manufacturing process?
Answer: Not for about 20 years after the original patent filing date.
3. Could they make some other product and take it through i, ii and phase iii trials?
Answer: Sure, be my guest. However, if it’s a dendritic therapy, they can’t use DCVax trial data to shortcut their safety claims or efficacy claims for several years.
4. Do most biologic and drug companies want to endlessly select their own target antigens or utilize their own small molecules instead of using autologous therapy, and do they all want a little lucrative niche with their own prized molecule, antigen target or other silver bullet that maintains the funds rolling in but keeps real cures forever at bay because they are each only dealing with part of the problem?
Answer: Yes, many companies want to keep that cynical economic paradigm alive by building single antibody drug conjugates with chemo or mRNA peptide therapy that tries to select their own antigen bundle then adds an unnecessary step of trying to get the dendritic cells in the body to manufacture and express these antigens. Many would like to put a cure out of reach by dividing up the antibodies and t-cell types amongst various companies, effectively guaranteeing tumor escape.
5. Does DCVax target all tumor antigens of each particular patient with Dendritic cells that directly express to a very broad spectrum of cytotoxic and helper t-cells whilst indirectly thus also creating an army of similarly varied antibodies, that, working together, minimize tumor escape?
Yes.
What chemotherapy does to t-cells and b-cells. ChatGPT
Yes, chemotherapy can indeed suppress both T cells and B cells, as it affects rapidly dividing cells, which include various types of immune cells. Chemotherapy drugs target not only cancer cells but also normal cells that have high turnover rates, such as immune cells in the bone marrow and lymphoid tissues.
The suppression of T cells and B cells can lead to immune system impairment, reducing the body's ability to mount effective immune responses against infections and cancer.
Further reading:
This additional explanation from ChatGPT:
Activated T cells play a crucial role in directing B cells to produce antibodies specific to cancer antigens through a process called T cell help. Here's how it works:
1. **Recognition of cancer antigens:** Dendritic cells present cancer antigens to T cells, activating them. Activated T cells recognize specific cancer antigens presented by dendritic cells through their T cell receptors.
2. **Activation of B cells:** Activated T cells release cytokines, such as interleukin-4 (IL-4) and interleukin-21 (IL-21), which provide signals necessary for B cell activation and differentiation. These cytokines stimulate B cells to proliferate and differentiate into plasma cells, which are responsible for producing antibodies.
3. **Induction of class switching and affinity maturation:** T cells also provide signals that induce class switching in B cells, allowing them to produce different types of antibodies (e.g., IgG, IgA, IgE) with specialized functions. Additionally, T cells help B cells undergo affinity maturation, a process involving somatic hypermutation that improves the affinity of antibodies for their target antigens.
4. **Selection of high-affinity B cells:** Through interactions with T follicular helper (Tfh) cells within specialized areas of lymphoid tissues called germinal centers, B cells undergo selection based on the affinity of their B cell receptors for the cancer antigens. B cells with higher affinity for the antigen receive stronger signals from Tfh cells and are preferentially selected for further differentiation into plasma cells or memory B cells.
Overall, activated T cells provide essential signals and guidance to B cells, ensuring the production of high-affinity antibodies specific to cancer antigens. This coordinated interaction between T and B cells is crucial for generating an effective immune response against cancer.
And finally, on the topic of memory B cells related to this process, ChatGPT points out:
Additionally, during affinity maturation, B cells undergo somatic hypermutation, resulting in the generation of B cells with higher affinity for the cancer antigens. These B cells, known as memory B cells, have a longer lifespan and remain in circulation even after the initial immune response subsides.
The presence of memory B cells ensures a faster and more robust immune response upon re-exposure to the same cancer antigens in the future. If cancer cells reappear, memory B cells can quickly differentiate into antibody-producing plasma cells, leading to a rapid and specific antibody response that contributes to the elimination of cancer cells. Thus, B cell memory formed through this process provides long-term immunity against cancer recurrence.
And here chatGPT explained how the indirect activation of B cells (via DC expression to t-cells) to create relevant antibodies then helps to improve the fight against the cancer.
The antibodies formed through this process contribute to a more effective response against cancer in several ways:
1. **Direct targeting:** Antibodies can directly bind to cancer cells, marking them for destruction by other immune cells such as macrophages and natural killer cells through a process called antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated cytotoxicity.
2. **Neutralization of cancer-promoting factors:** Antibodies can bind to cancer-promoting factors such as growth factors or receptors, preventing them from interacting with their targets and inhibiting cancer cell proliferation and survival.
3. **Enhancement of antigen presentation:** Antibodies can bind to cancer antigens, forming immune complexes that are more efficiently recognized and processed by dendritic cells. This enhances the presentation of cancer antigens to T cells, leading to a stronger T cell-mediated immune response against cancer.
4. **Recruitment of other immune cells:** Antibodies can recruit other immune cells, such as macrophages and neutrophils, to the tumor site through the activation of complement or Fc receptors, further enhancing the immune response against cancer.
Overall, the antibodies produced through the activation of B cells by dendritic cells play a crucial role in coordinating and amplifying the immune response against cancer, leading to more effective elimination of cancer cells.
And here was its answer to my follow up question as to how B cells with the correct receptor are indirectly activated by dendritic cell antigen expression to t-cells. You’ll obviously need to read it all the way through.
Dendritic cells indirectly activate B cells with appropriate receptors through a process called antigen presentation. When dendritic cells encounter cancer antigens, they internalize and process these antigens. Then, they present small fragments of these antigens, called peptides, on their cell surface using molecules called major histocompatibility complex (MHC) molecules.
T cells constantly survey these MHC-peptide complexes presented by dendritic cells. If a T cell recognizes a cancer antigen presented by a dendritic cell, it becomes activated. Once activated, the T cell releases signaling molecules, such as cytokines, that can stimulate nearby B cells. These cytokines can trigger B cell activation, leading to their proliferation and differentiation into plasma cells, which produce antibodies specific to the cancer antigens. So, dendritic cells indirectly activate B cells with appropriate receptors by presenting cancer antigens to T cells, which then release signals to stimulate B cell activation.
This is also kind of interesting. From a conversation I had with ChatGPT
B cells learn which antibodies to produce through a process called affinity maturation. Initially, when dendritic cells present antigens to T cells, B cells with receptors that can recognize those antigens are activated. These activated B cells then undergo clonal expansion and differentiation into plasma cells, which produce antibodies specific to the presented antigens.
During affinity maturation, B cells undergo somatic hypermutation, a process where the DNA encoding the antibody variable regions undergoes random mutations. B cells with mutations that result in higher affinity for the antigen are positively selected, while those with lower affinity are negatively selected. This process allows B cells to produce antibodies with higher affinity for the specific cancer antigens (originally) presented by dendritic cells (to the t-cells), leading to a more effective immune response against cancer.
Switching the arms increased blood antibody levels by as much as fourfold, the scientists found. The results were published in The Journal of Clinical Investigation.
The immune response was stronger against both the original coronavirus and against the Omicron variant, which emerged roughly a year after the authorization of the first Covid vaccines.
“It’s a consistent, statistically significant effect; is pretty sizable; and it seems to be quite durable,” Dr. Curlin said.
The results appear at first to contradict those from a German study last summer showing that rolling up the same sleeve each time might yield a better immune response. But that study measured antibody levels only two weeks after the second dose.
In that period, the new study also found similar results. But the pattern slowly shifted over the subsequent months to higher antibody levels in those who alternated arms. — NYT February 6, 2024
Your post looks like you are on the wrong message board. L hasn’t been available for commercial sales/production yet. Dummkopf.
Imo, there is a reason they didn’t expand beyond 1000 available capacity annually with the manual method, and that is because they expect to transition to Eden by the time manual capacity is reached. It’s far easier to keep expanding rapidly after that.
I think you were talking about the other poster.
This is the MHRA. It’s calendar days.
Car-T therapy: Can take up to a year for all facets of immune system to return. B-cells themselves can get back up to baseline in about 90 days. Imo. I think this was scientifically controversial until recently.
Personally if I were to hazard a guess, I’d agree with Ex that the King has B-cell lymphoma. B cell cancers are perfect for Car-T, because you can wipe out all the B Cells with and without cancer. You can’t do that with other types of cancers.
Such therapy would leave the King vulnerable to infection, which would explain why he is avoiding contact with the public.
Eventually, if that were the case, the Kings immunity could be reestablished after treatment cycles concluded.
We don’t “know” but the likelihood is the electronics are already present for DCVax-Direct, which requires no lysate, different precursors and less maturation, because the goal is partial maturation for DCVax-Direct.
You are arguing out of both sides of your mouth. In the post I’m responding to you totally ignore:
1. That the Eden system is specifically designed for DCVax specifications.
2. That the Eden system will be proven to reach those end product specifications, imo.
3. That the Eden system is patented, and will be further patented to outline the optimization.
4. That NWBO owns Flaskworks.
5. That the end product is DCVax-l.
6. That the end product is protected by biologic exclusive use for ten years from time of approval.
7. That there is data exclusivity for the phase iii trial (safety and efficacy) for five years.
8. That other autologous whole lysate pulsed dendritic therapies are at best several years from obtaining approval.
If you research what “value proposition” means, you’ll find the next step is marketing that clearly to target audiences. HM is just trying to look like a fortune teller when NWBO follows (likely) approval with a “slide deck.” Of course they will if the reg review goes well. Wouldn’t be surprised to see a great slide deck around late May, or perhaps much sooner.
I think it is a stretch as well, but if it was an inoperable cns tumor, large needle biopsy guided by clear point could make L feasible. Again, though, odds are it is a different type of cancer.
Figure it out. Ask yourself, who has been following and trying to explain court matters.
HM wrote it was from attorney filings.
From the derivative trial, “attorney filings,” according to HM (18hours ago) I’m not certain what date this filing statement was made. Nevertheless, I believe it is profound.
”….yesterday's call, the Company is at a mission-critical point in its existence.
Over the next three months, the Company will be preparing for and undergoing detailed inspections of the contract research organizations ("CROs") that managed the trial, the Sponsor, the Trial Master File, a number of individual trial sites selected by the regulator from among the 94 sites that participated in the trial, the GMP facility and manufacturing information.
This is a Herculean task, one on which the value proposition of the Company rests.”
It was called hospital exemption, and it turned out to be very very difficult to utilize, because you had to negotiate reimbursement with each German district. Also, the German regulator appeared to want automatic closed system manufacturing.
The compassionate program worked well in Great Britain however.