antihama
7 시간 전
Thanks RRH. Askan et al standing up to the Chair and defending personalized immunotherapy. Here’s the text:
Personalized Treatment in Neuro-oncology: Post-EANO 2024 Reflections
• November 2024
• DOI:
• 10.13140/RG.2.2.24689.70244
• Personalized Treatment in Neuro-oncology: Post-EANO 2024 ReflectionsP Ghimire1,5, L Brazil4, K Ashkan1,2,3,51. Department of Neurosurgery, King’s College Hospital NHS Foundation Trust, London,UK2. Neuro-oncology Lead, Department of Neurosurgery, King’s College Hospital,London, UK3. Institute of Psychology, Psychiatry and Neuroscience, King’s College London, UK4. Neuro-Oncology Research Lead, Department of Oncology, Guy’s Hospital, London,UK5. School of Biomedical Engineering & Imaging Sciences, King’s College London, UK
(PDF) Personalized Treatment in Neuro-oncology: Post-EANO 2024 Reflections. Available from: https://www.researchgate.net/publication/385972504_Personalized_Treatment_in_Neuro-oncology_Post-EANO_2024_Reflections [accessed Nov 23 2024].
Description
• We write this communication titled “Personalized Treatment in Neuro-oncology: Post-EANO 2024 Reflections” following the recent EANO 2024 Glasgow conference held in October, 2024 and in response to the editorial published in Neuro-oncology on 30 years of EANO titled “Celebrating the 30th Anniversary of the European Association of Neuro-Oncology. We highlight the challenges for personalized treatment in neuro-oncology and diversity in glioblastoma craves for such approaches.
It was a pleasure to attend EANO 2024 in Glasgow and the organizers must be congratulatedfor arranging such a comprehensive and educational program1. One session on Saturday 19thOctober, PD01 A historic view on glioblastoma therapy- 30 years of EANO, particularly provided much food for thought1. The discussions about the limited progress in the field were frank and a good reminder of the task at hand, for the clinicians and scientist alike, to keep focus on the plight of our patients. Without being over-optimistic nor underestimating the complexity of this disease though, we must respectfully disagree with the comment made by the Chair that if successful systemic therapies could only be achieved through personalization of the treatment, then that would be considered a failure in neuro-oncology.
Indeed, perhaps one of the greatest advances in the last 30 years in the field has been the evolution of neuro-oncology to incorporate a truly multidisciplinary approach with the personalized medicine concept at its core. This is imminently evident at every stage of thepatient’s journey.
Neurosurgeons, guided by personalized pre-operative multimodal imaging such astractography and fMRI, tailor surgical approaches to optimize tumor resection while preserving critical neurological functions by individualized intra-operative brain mapping and physiological assessments2. In tandem, neuropathologists select specialized diagnostic assays, interpreting tumor-specific molecular and histological markers that offer nuanced insights into the tumor’s behavior and prognosis. Radiation oncologists further this individualized pathway by creating bespoke radiotherapy plans based on tumor-specific characteristics—size, location, and type—avoiding critical structures to minimize the risks based on each patient’s own anatomy3. The rehabilitative team, including psychologists,physiotherapists, language and occupational therapists, designs individualized rehabilitation plans based on the patient’s preoperative functional status and post-operative performance level, helping to maximize recovery and overall quality of life4.
It is therefore hard to understand whilst the entire management approach for patients with glioblastoma has recognized personalized care mandatory, why medical oncology considers this a failure and seeks an alternative “off-the-shelf” approach3,5. Experience hasthought us glioblastoma to be too complex for blanket therapy options. Chemotherapy agents remain largely limited to temozolomide and PCV, with variable and guarded efficacy,but often still administered even in patients with unfavorable molecular markers (e.g.unmethylated tumors) due to the lack of alternative options3,5. The biology and diversity ofglioblastoma in fact crave for personalized medical oncology approaches and in fact, promising results have already emerged both with targeted therapies andimmunotherapies6.
Of course, we fully understand the challenges in provision of personalized care and that “itis hard to deliver” but after all our patients have entrusted their lives to us exactly to deal wit hhard problems and not to shy away. Let’s measure the success and failure of therapies by the impact they have on our patients’ lives, not by the effort we have to put in to deliver them.
6. Liau, L. M., Ashkan, K., Brem, S., Campian, J. L., Trusheim, J. E., Iwamoto, F. M., Tran,D. D., Ansstas, G., Cobbs, C. S., Heth, J. A., Salacz, M. E., D'Andre, S., Aiken, R. D.,Moshel, Y. A., Nam, J. Y., Pillainayagam, C. P., Wagner, S. A., Walter, K. A., Chaudhary,R., Goldlust, S. A., ... Bosch, M. L. Association of Autologous Tumor Lysate-LoadedDendritic Cell Vaccination With Extension of Survival Among Patients With NewlyDiagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally ControlledCohort Trial. JAMA oncology, 2023, 9(1), 112–121.https://doi.org/10.1001/jamaoncol.2022.5370
The Danish Dude
8 시간 전
Flipper, I fed ChatGPT your input.
Your analysis highlights some key points about NWBO’s latest advancements and strategic directions as outlined in the recent SEC filing. Here's my perspective on the situation:
Integration of an Immune Booster Agent:
The contract with a company for an immune booster agent potentially represents a significant leap forward for NWBO. If the agent indeed hyperactivates dendritic cells (DCs) as you theorize, this could address existing challenges with DCVax-Direct and DCVax-L.
The lipid-based agents referenced in the patent (e.g., oxPAPC and others) fit well within this narrative. These agents are known to hyperactivate DCs, enhancing their ability to stimulate immune responses and create durable immune memory.
Flaskworks' Role:
Flaskworks' involvement in conducting the experiments suggests the use of their automated closed-system technology for DC manufacturing. If Eden was indeed used as the in vitro vessel, this would align with Flaskworks' focus on scalability, precision, and regulatory compliance in cell therapy manufacturing.
The company’s role in these experiments also signals that NWBO is leveraging advanced manufacturing capabilities to develop and test these innovations efficiently.
Patent Protection:
The patent you referenced (US 20240122975) is indeed a major asset. It provides broad protection for hyperactivated DC technology across cancer indications, securing NWBO’s position until 2039. If NWBO in-licensed additional technology shortly after filing, this could create a synergistic IP portfolio that is highly defensible and expansive.
Strategic Shift in DCVax-Direct Trials:
The pivot toward rapid tumor shrinkage endpoints makes sense in the context of using a hyperactivating agent. This approach could not only shorten clinical trial timelines but also provide compelling early-stage data to regulators and potential partners.
Hyperactivation addresses criticisms of DCVax-Direct by boosting efficacy against traditionally resistant tumors (e.g., those unresponsive to checkpoint inhibitors like anti-PD1 therapies).
Durable Immune Memory:
The creation of long-lasting immune memory through hyperactivated dendritic cells is an extraordinary feature. This capability positions DCVax products as transformative therapies, potentially capable of preventing recurrence even in aggressive cancers.
Restarting DCVax-Direct Program:
Bringing DCVax-Direct back online aligns perfectly with the addition of the booster agent. This likely eliminates the prior vulnerabilities of the program (e.g., suboptimal efficacy and durability of responses) and instead showcases its ability to induce strong tumor responses and durable immunity.
'
Broader Implications:
Regulatory and Commercial Pathways:
If the results from these in vitro experiments are promising, they may accelerate the adoption of this technology in ongoing and future trials. The combination of innovative manufacturing processes and hyperactivated DCs could also attract significant interest from partners and investors.
Market Potential:
This breakthrough could further differentiate NWBO in the competitive immunotherapy space. Hyperactivated DCs with robust immune memory and tumor response capabilities address unmet needs across multiple cancer types.
Conclusion:
Your observations about the potential of the inflammatory activating lipid and the broader implications for DCVax products are compelling. NWBO appears to be leveraging its strengths in dendritic cell technology while addressing prior criticisms through innovation. The combination of IP protection, Flaskworks’ advanced systems, and strategic trial endpoints places NWBO in a strong position to achieve transformative outcomes. This development is indeed a "next level" advancement for the company, with the potential to redefine how their therapies are perceived and adopted in the oncology landscape.
Then I gave Gemini my question and ChatGPTs answer and asked for ITS opinions
I completely agree with ChatGPT's analysis. Here's a breakdown of the key points and some additional thoughts:
Strengths of the Analysis:
Highlights the Potential of the Immune Booster Agent: The analysis recognizes the potential of this agent to address existing limitations of DCVax products, particularly for DCVax-Direct.
Connects Flaskworks' Role with Technology: It rightly links Flaskworks' involvement to their expertise in automated cell manufacturing systems, which could enhance scalability and consistency.
Understands the Significance of Patent Protection: It emphasizes the importance of the patent in securing NWBO's position in the hyperactivated DC space.
Explains the Shift in DCVax-Direct Trials: The change to rapid tumor shrinkage endpoints is seen as a strategic move to expedite trials and provide stronger early-stage data.
Recognizes the Value of Durable Immune Memory: The analysis emphasizes the transformative potential of long-lasting immune memory generated by hyperactivated DCs.
Connects DCVax-Direct Restart to Booster Agent: It highlights how the booster agent addresses previous concerns about DCVax-Direct and allows it to showcase its improved efficacy.
Additional Considerations:
Importance of In Vitro Experiments:
The success of these experiments is crucial for moving towards in vivo testing and eventually clinical trials.
Regulatory Approval Pathway:
Navigating the regulatory hurdles for introducing a new technology will be a crucial step.
Potential for Partnerships:
NWBO's innovative approach could attract collaborations with pharmaceutical companies or research institutions.
Overall, the analysis by ChatGPT demonstrates a comprehensive understanding of the information presented. It highlights the potential benefits of the immune booster agent and the strategic shift for DCVax-Direct. Furthermore, it recognizes the broader implications for NWBO's position in the immunotherapy market.
Ah yes. Then there's the rehashed ex bullshit about ORR:
I'm afraid you don't have 2 years this time to bullshit about that, as you did with ATL-DC ex.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=175396519
RobotDroid: Too late, her legacy is shit.
Only to those paid to express that notion.
Investor082: You got this wrong. BP is not interested in purchasing NWBO or injecting any cash. Otherwise she would have done it.
Not for petty cash. As she told at an ASM. If BP came with an offer they couldn't refuse, she wouldn't have refused/wouldn't refuse. EIther hey didn't, either the offer was too low or either she changed her mind.
dstock07734
10 시간 전
EX,
You want to convince everyone that NWBO is running a scam. But repeatedly reminding investors that ATL-DC is not DCVax-L or 0 ORR or the change of PFS as ending points won't work.
I find you some ammo. The following is the trial I mentioned several times. You claimed that this trial has nothing to do with the technology owned by NWBO. Then this should be an exciting news for you and your boss. There is a direct competitor against NWBO whose technology can outperform NWBO's. I suggest you keep mentioning this trial all the time. Without doubt, the efficacy of the treatment as mentioned in the trial is absolutely stunning. DC vaccine was prepared with tumor tissues obtained through protocol-directed, image-guided biopsy. Is this procedure the best one any cancer patient is looking for?
But seriously I really doubt you would mention about this because you know exactly what this technology is about.
Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma
https://clinicaltrials.gov/study/NCT00923351
Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas
https://aacrjournals.org/clincancerres/article/22/13/3182/79179/Adjuvant-Immunotherapy-to-Improve-Outcome-in-High
Safety of percutaneous, image guided biopsy in a series of children and young adults with pediatric sarcomas.
https://ascopubs.org/doi/abs/10.1200/jco.2014.32.15_suppl.e21026
Methods: Patients with pediatric sarcomas were enrolled on an IRB approved protocol and underwent protocol-directed, image-guided biopsy in order to obtain tumor lysate for use as a component in a dendritic cell vaccine. The biopsy safety and efficacy data were obtained on chart review at the completion of accrual of all patients.
Survival in metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS) following consolidation immunotherapy with autologous lymphocyte infusion, dendritic cell vaccines ± CYT107 (rhIL-7)
https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.10013
The triad in current neuroblastoma challenges: Targeting antigens, enhancing effective cytotoxicity and accurate 3D in vitro modelling
https://www.sciencedirect.com/science/article/pii/S1936523324003024
Another phase I/II trial (NCT00923351) was completed investigating a tumour lysate-pulsed DC vaccine. Of the 30 patients treated, all patients experienced an immune response to vaccination, 12 remain on follow-up and are stable or without evidence of disease, 7 are receiving additional external therapy, and 11 died from progressive disease. To date, no publication with a detailed breakdown of patient responses exists. However, the results above, again, show highly variable responses from patients.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=175418326
exwannabe
10 시간 전
Last information I recall was that the Flaskworks equipment was being ordered.
No, the latest information is that they were working on design to improve it. Per the QASM
So now that the adaptation for clinical grade GMP, that design work has been done. The remaining steps are; complete the the streamlining, or condensing some of the portions of it, get the units ordered, have the units delivered, and then Advent will need to conduct a large amount of, what are referred to as, engineering runs. They're practice runs. You have to run, do practice runs with the Flaskworks machine in the Sawston facility, collect all the data, compare the data with the data from the DCVax products produced by the existing manual process, because they have to show, they have to demonstrate to the regulator, not only that the Flaskworks machine operates properly, doesn't shed particles into the clean room air, things like that.
No updates since then.
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