$nwbo @alphavestcap @ATLnsider moffitt.org/for-healthcare-p… x.com/d_stock07734/status/20… The NATASHA trial (NCT05325632) is a phase 2 clinical trial evaluating HER2-directed intratumoral dendritic cell (DC1) therapy prior to standard neoadjuvant chemotherapy (paclitaxel, trastuzumab, and pertuzumab) for stage I-III HER2-positive breast cancer. Results have shown robust radiologic tumor responses and a high pathologic complete response (pCR) rate.📷OncLive  2Trial OverviewObjective: To evaluate whether integrating a personalized, autologous HER2-sensitized DC1 vaccine with neoadjuvant therapy can boost anti-tumor immune responses, improve pathologic complete response rates, and potentially de-escalate aggressive cytotoxic chemotherapy requirements. Lead Institution: Moffitt Cancer Center (Tampa, Florida). Study Design: A non-randomized, open-label trial.📷Moffitt  2Key Findings and EfficacyData from the initial trial phases demonstrated significant clinical benefits and immune activation:📷ASCO Publications  2Pathologic Complete Response (pCR): Trial data reported that a majority of patients who completed surgery achieved a pCR.📷OncLive Tumor Regression: Patients exhibited significant reduction in primary tumor burden. Furthermore, the therapy successfully suppressed metastasis-initiating cancer cells (MICs) from disseminating to distant organs like the bone marrow.📷National Institutes of Health (.gov)  1 Immune Modulation: Immune monitoring demonstrated that intratumoral DC1 delivery enhanced local tumor immune infiltration (CD4 , CD8 T cells, and Natural Killer cells) while properly shifting systemic anti-HER2 T cell responses.📷ASCO Publications  2Safety and TolerabilityThe addition of the DC1 vaccine to standard neoadjuvant therapy was found to be safe and well-tolerated, avoiding systemic toxicity typically seen with heavy chemotherapy. Side effects were primarily manageable and constitutional (indicative of immune activation), including:📷ASCO Publications  3Chills Fatigue Diarrhea and nausea HeadachesTo track further developments, updates, and presentations (such as Poster 384), you can review trial specifics on Moffitt Presentations at ASCO or check the ClinicalTrials.gov entry for NCT05325632. Intratumoral dendritic cell (DC1) therapy prior to neoadjuvant chemotherapy in HER2-positive breast cancer (NATASHA trial) Poster 384 Hyo Han, MD Post See new posts Conversation Andrew Caravello, DO@andrewcaravello🌌 The Final Frontier of Cancer: How $NWBO #DCVax and DoD-Backed Dendritic Cells Are Rewriting the Future of Leptomeningeal Disease 📷 TLDR Leptomeningeal disease (LMD) in breast cancer is one of oncology’s deadliest diagnoses, with survival of only 6–12 weeks untreated and 2–4 months on intrathecal chemotherapy. Even with intrathecal trastuzumab, HER2-positive patients reach just ~10.5 months median survival. Moffitt Cancer Center and Roswell Park — with U.S. Department of Defense backing — are running the first-in-human trial of intrathecal dendritic cell vaccination (NCT05809752). This platform uses αDC1 dendritic cells primed with HER2/HER3, paired with chemokine modulation and checkpoint inhibition, injected directly into cerebrospinal fluid. It is designed to bring adaptive immune memory into a compartment long thought unreachable. What makes it transformative is not only the science, but the ownership. NWBO controls the patent moat: exclusive rights to whole tumor lysate loading, αDC1 polarization, and automated manufacturing via Eden/EDITH. No competitor can commercialize this approach without crossing NWBO’s IP. The FDA’s 2025 expedited guidance opens fast lanes through RMAT designation, Accelerated Approval based on biomarkers or intermediate outcomes, and acceptance of real-world evidence (RWE) for both approval and post-market follow-up. With DoD sponsorship, the trial also aligns with the Commissioner’s National Priority Voucher (CNPV), cutting review times and adding asset value. In short: NWBO owns the immune operating system, the FDA has built the regulatory runway, and federal agencies have raised the flag. If the intrathecal trial shows survival beyond historical baselines, this platform is positioned for accelerated commercialization under exclusive control. 📷 Leptomeningeal disease is cancer’s final frontier. When breast cancer cells seed the meninges and cerebrospinal fluid, the outlook is dire. Patients deteriorate r🧩e prognosis is even grimmer. For HER2-positive disease, intrathecal trastuzumab has nudged median survival closer to a year, but it is still a ceiling that most never reach. The biology explains why. The cerebrospinal fluid is an immune desert: innate immune activity is present, but adaptive T-cell memory is absent. The blood–brain and blood–CSF barriers block systemic drugs. Cancer cells, once inside, are shielded from most therapies. The result is an almost uniformly lethal sanctuary. Guidelines are blunt: enroll these patients in clinical trials. Standard therapies are not enough. Only innovation will bend the curve. 📷 The Roswell Foundation 📷 The Moffitt Backbone 📷 If Roswell Park gave dendritic cell vaccination its intellectual architecture, Moffitt Cancer Center became its proving ground in breast cancer. Here, under the leadership of Dr. Brian Czerniecki, a series of trials began to show how dendritic cells could reshape outcomes in ways standard ther3️⃣the TCHP regimen). Three vaccine delivery strategies were compared: intranodal only, alternating intratumoral plus intranodal, and an extended alternating arm. The results were striking. •Pathologic complete response (pCR): •Intranodal only: ~42.8%. •Alternating: ~66.6%. •Extended alternating: ~72.7%. These numbers mattered. In cutting-edge HER2 trials like TRAIN-2 or KRISTINE, pCR rates hovered between 50–60%. By layering dendritic cell vaccination on top of standard care, Moffitt pushed those numbers significantly higher. Since pCR in HER2 disease correlates strongly with long-term survival, the implication was clear: dendritic cells were amplifying the curative poten🧪g patients from the harshness of full-dose regimens — while keeping control of the disease. This reflected a maturing philosophy: dendritic cells were not just adjuncts, they could become central players, enabling safer and smarter cancer care. Meanwhile, Moffitt also turned its gaze to triple-negative breast cancer (TNBC), the most unforgiving subtype. Here, chemotherapy often leaves patients with residual disease after neoadjuvant treatment, and those residual tumors are ominous predictors of relapse. To address this, Moffitt launched a Precision DCV trial (MCC-23142). Instead of whole tumor lysate, which provides breadth, this trial uses sequencing to identify patient-specific neoantigens. Selected peptides are loaded onto dendritic cells, aiming to create a personalized vaccine to mop up residual disease and reduce relapse risk. It’s a more focused approach, narrower than lysate, but a rational experiment to test whether sequencing-guided precision could give TNBC patients an immunologic edge. Together, these trials formed a backbone: •They proved dendritic cells could be safely manufactured and delivered. •They showed clinical signals of efficacy — higher pCR rates, stronger immune infiltration, the possibility of reducing chemotherapy. •They tested breadth (lysate-based HER2) and precision (neoantigen-selected TNBC). •And they confirmed HER2 and HER3 were not just druggable targets, but teachable targets for the immune system. With Roswell laying the intellectual foundation and Moffitt building clinical scaffolding, the stage was set for the boldest move yet — into the cerebrospinal fluid itself. 📷 The Leap Into the CSF 📷 In August 2023, Moffitt Cancer Center, Roswell Park, and Memorial Sloan Kettering launched NCT05809752 — the first human trial of intrathecal dendritic cell vaccination for leptomeningeal disease (LMD) from breast cancer. This trial is as audacious as it sounds. For the first time, dendritic cells — the immune system’s master teachers — are being injected directly into the cerebrospinal fluid (CSF), where malignant cells spread across the brain and spinal cord. The vaccine is made from each patient’s monocytes, harvested by leukapheresis, matured into type-1 polarized cDC1s, and pulsed with HER2 and HER3 antigens. Then, through an Ommaya reservoir surgically implanted into the ventricle, the cells are delivered intrathecally once a week for up to 12 weeks. The dose escalates from 1 million dendritic cells to 50 million per 4️⃣ts with untreated leptomeningeal disease live 6–12 weeks. With intrathecal methotrexate or cytarabine, survival is 2–4 months. For HER2-positive disease, intrathecal trastuzumab improved survival to ~10.5 months in the best trials. But TNBC patients, who have no targeted intrathecal option, often survive only weeks. The bar is low, and the need is desperate. The intrathecal DC vaccine is designed to change the equation. Dendritic cells act as teachers, showing HER2 and HER3 antigens to T cells. But they don’t act alone. Patients also receive a chemokine modulatory regimen (CKM) — rintatolimod (Ampligen, a TLR3 agonist) and interferon-α2B — to flood the CSF with T-cell rec🌊he loudspeaker. •Checkpoint inhibition = the brake release. Preclinical studies showed that this combination could cure most mice with HER2 leptomeningeal disease. Injected dendritic cells educated T cells, CKM attracted them into the CSF, and checkpoint inhibitors prevented suppression. Tumors disappeared, and animals resisted re-challenge — proof of immune memory. In humans, safety is paramount. The CSF is a closed compartment, and regulators demanded dose escalation to ensure no catastrophic inflammation or intracranial pressure. As of early 2025, the first patients have tolerated the lowest doses without dose-limiting toxicities. Cytokine analysis of CSF shows early IFN-γ signals — the first hints that the immune desert can be reprogrammed. The stakes are stark: if patients begin surviving beyond 3–4 months, it will already surpass the historic baseline. If survival approaches trastuzumab’s 10.5 months, it will be a breakthrough. If durable immune memory emerges — patients living years with disease control — it will redefine leptomeningeal disease entirely. This is more than a trial. It is a proof of concept that immunotherapy can penetrate the central nervous system, teaching the immune system to fight in the one place cancer has always had sanctuary. 📷 The National Dimension 📷 This intrathecal dendritic cell vaccine trial is not just an academic experiment. It carries the seal of the United States Department of Defense (DoD), which co-funds the study through its Congressionally Directed Medical Research Program. That involvement is not symbolic. It signals that the U.S. government views this as a matter of strategic importance. The DoD has a track record here. It previously funded Roswell Park’s αDC1 breast cancer vaccine trial (NCT04348747), which pulsed dendritic cells with HER2/HER3 and paired them with pembrolizumab. That trial helped prove feasibility and was one of the stepping stones to Moffitt’s current effort. Why does the military care? Because TNBC disproportionately affects younger women, including service members and their families. Because leptomeningeal disease is almost uniformly fatal. And because building immune system infrastructure is increasingly seen as part of national preparedness. The DoD imprimatur means this trial has both scientific and political weight. It is not just a promising therapy; it is a national mission. That point was underscored when Moffitt leaders, including Dr. Brian Czerniecki, traveled to Capitol Hill in 2025 to meet with federal stakeholders. Their agenda: to highlight the urgency of dendritic cell immunotherapy in solid tumors and secure sustained government support for infrastru5️⃣ created the perfect regulatory runway. The new framework emphasizes: •Platform Consistency: The FDA now recognizes that therapies like dendritic cell vaccines can operate as platforms. Whether delivered intradermally for glioblastoma (DCVax-L), intratumorally for breast cancer (NATASHA, DecipHER), or intrathecally for LMD, the core mechanism — αDC1 maturation plus antigen pulsing — is conserved. That consistency supports bridging approvals. •Mechanistic Validation: Regulators now expect biomarker evidence that the therapy is doing what it claims. This trial is built around exactly that: CSF cytokine assays, single-cell RNA sequencing, immune cell infiltration studies. Ev🛡️mall Phase 1 sample. •National Priority Voucher (CNPV): With #DoD backing and an indication as lethal as leptomeningeal disease, this program qualifies for the Commissioner’s National Priority Voucher. That could compress FDA review timelines from years to months — a lifeline for patients who simply don’t have time. The alignment is uncanny. The science, the government, and the regulator are all moving in the same direction: toward accelerated approval of platform-based immunotherapies that address urgent national health priorities. 📷 The Patent Moat Meets the New Framework What makes this moment different is not only the science, but the ownership. Northwest Biotherapeutics has secured the two halves of the dendritic cell vaccine puzzle: •Antigen breadth: Exclusive rights to whole tumor lysate DC loading — the only method that ensures every patient’s full tumor signature is captured, preventing escape. •Immune potency: The αDC1 polarization engine, licensed from Roswell, that guarantees IL-12–driven, Th1-polarized dendritic cells capable of durable T-cell instruction. •Manufacturing scale: Control of Flaskworks’ Eden and the EDITH automation patents, which solve the FDA’s biggest bottleneck — reproducibility and consistency in cell therapy manufacturing. This means no competitor can legally or practically commercialize a true DC vaccine platform without running straight into NWBO’s IP. The new FDA draft guidance of 2025 makes this even more consequential. It emphasizes that regenerative medicine products, including cellular immunotherapies, can: •Qualify for RMAT designation on the basis of early-phase clinical data if there’s serious unmet need. •Use Accelerated Approval pathways based on surrogate endpoints, such as immune biomarkers or intermediate clinical outcomes, instead of waiting for long survival curves. •Rely on real-world evidence #RWE, including external controls or post-market data, to support both approval and post-approval obligations. Layer this onto NWBO’s existing data: •Phase 3 GBM (DCVax-L) showing survival tail and long-lived responders. •Multiple Phase 2 programs in breast and ovarian cancer. •Real-world Specials data already being collected 🏰iority Voucher #CNPV initiative. That voucher can shave months off FDA review and add value to NWBO’s balance sheet in its own right. In plain terms: NWBO holds the code, the patents, the manufacturing rights, and now operates inside a regulatory framework explicitly designed to reward platform-level, mechanism-driven, RWE-supported therapies. Others may experiment, but only NWBO can commercialize. And under the new rules, that commercialization can move faster than ever before. 📷 The Immune Logic Behind the Platform At the heart of this approach is dendritic cell physiology. Dendritic cells are not fighters, they are teachers. Their role is to take up antigen, chop it into peptides, load them onto MHC molecules, and migrate to lymph nodes. Once there, they provide the three signals needed to activate T cells: 1.Antigen presentation (the lesson plan). 2.Costimulation (CD80/CD86 → CD28, the permission slip). 3.Cytokine programming (IL-12, the curriculum bias toward Th1 killers). The αDC1 polarization method perfected by Kalinski is the keystone. By maturing monocytes under GM-CSF IL-4, then driving them with TNF-α, IFN-α, IFN-γ, and Poly-ICLC, the cells secrete IL-12p70 at high levels. IL-12 is non-negotiable: without it, T cells drift toward tolerance or exhaustion. With it, they polarize into Th1 CD4 helpers and CD8 cytotoxic lymphocytes, capable of sustained, tumor-directed aggression. This is why early DC vaccines often disappointed — they used immature DCs that secreted IL-10 or little cytokine at all, teaching tolerance instead of immunity. The αDC1 design fixed that flaw. 📷 Breadth and Precision Together How should the immune curriculum be written? Two approaches are on the table: •Whole Tumor Lysate (DCVax-L, Roswell licensing, NWBO patents): This provides breadth. Every antigen, every clonal and subclonal epitope, including splice-derived neoantigens, gets presented. Tumors can’t escape by simply shedding one target. The tradeoff is noise — the immune system may waste effort on irrelevant peptides unless potency thresholds are enforced. •Neoantigen Selection (Precision DCV, MCC-23142): This provides precision. Sequencing identifies mutations likely to bind HLA and be immunogenic. Peptides are selected and pulsed onto DCs. The immune response is focused but narrower — escape risk is higher if predictions miss critical epitopes. The ideal future is a hybrid model: whole lysate for broad coverage, sequencing-based algorithms like #IRIS to highlight the most relevant targets, and monoclonal antibodies to paint those targets in vivo for redundancy. That triangulation — breadth plus precision plus painting — is what makes this platform a true immune operating system. 📷 The Immune Operating System What’s emerging is not a therapy, but an operating system. •αDC1 polarization is the kernel — the instructional engine. •Antigen input (lysate, sequencing, IRIS splicing data) is the code. •Boosters like Poly-ICLC or G100 are compilers, amplifying the lesson. •IL-7 (RevImmune’s CYT107) is the archive, preserving the trained memory pool. •Checkpoint inhibitors are the debugging tools, removing suppressive 🧬regulators mean when they say platform consistency — once the architecture works in one space, it can be replicated anywhere the terrain demands it. 📷 The Signal Fire The closing movement is a signal fire. A flare sent from one of the darkest places in oncology, the cerebrospinal fluid, announcing that the immune system can be taught to fight here too. If patients survive beyond three months, it beats history. If they reach trastuzumab’s 10.5-month mark, it redefines the standard. If immune memory carries some beyond a year, it proves the fortress can be held. But what makes this fire different is who holds the torch. NWBO controls the full patent moat: the αDC1 engine, the whole tumor lysate loading rights, and Eden/EDITH automation for global scaling. Others can run trials, but only NWBO can legally and practically commercialize this immune operating system. The FDA’s new 2025 guidance has lowered the drawbridge. Under RMAT designation and Accelerated Approval, immune biomarkers and intermediate outcomes can be enough to greenlight commercialization. Real-world evidence can fulfill confirmatory requirements. And with DoD backing, this trial is a prime candidate for the Commissioner’s National Priority Voucher (CNPV), compressing timelines and adding immediate strategic value. The science proves the system works. The patents ensure exclusivity. The FDA has paved the regulatory runway. The DoD has signaled national priority. Together, they turn a first-in-human trial into the opening act of a commercial rollout. This is no longer about single patients or single trials. It is about whether an immune operating system, locked by NWBO’s patents, can now travel the accelerated pathways to market under exclusive commercialization rights. And that is the way it is — the signal fire lit against the final frontier of cancer, now tethered to a patent-protected, voucher-ready, regulator-approved future. 📷 Sources Clinical Trials & Publications NCT05809752 – “A First in Human Dose Escalation of Dendritic Cell Vaccine Administered Intrathecally Primed Against HER2/HER3 in Patients With Leptomeningeal Disease From Triple-Negative Breast Cancer or HER2 Breast Cancer” (Moffitt Cancer Center, DoD collaborator). NCT04348747 – Roswell Park Phase 2 trial of αDC1 DCs pulsed with HER2/HER3 in breast cancer brain metastases and TNBC, funded by DoD CDMRP. NCT03387553 – Moffitt Phase 2 neoadjuvant HER2-pulsed αDC1 vaccines TCHP chemotherapy in HER2 ER- breast cancer. Published in npj Breast Cancer, 2025: Soliman H, Han HS, et al. PMID: 40048036. NCT05325632 (NATASHA) – Trial of HER2-DC vaccines with reduced chemotherapy in early HER2 breast cancer. MCC-23142 (Precision DCV) – Moffitt’s sequencing-based peptide-pulsed DCV trial for high-risk TNBC with residual disease. NCT01957956 – DCVax-L in newly diagnosed GBM, Phase 3. Publication: Liau LM, Ashkan K, et al. JAMA Oncology. 2022; PMID: 36394838. Kumarhekar et al., 2023 – Phase I/II intrathecal trastuzumab in HER2 leptomeningeal metastases, Neuro-Oncology. PubMed: 35948282. Regulatory Guidance FDA (Sept 2025) – Draft guidance: Expedited Programs for Regenerative Medicine Advanc🔥ional health security. EANO–ESMO 2023 Guidelines – Leptomeningeal metastasis management framework, Annals of Oncology, 2023. 📷 Disclaimer This content is for informational and educational purposes only. It is not medical advice, investment advice, or a solicitation. Clinical trial results are pending and subject to change. Always verify with , peer-reviewed publications, and official regulatory guidance. #NWBO #DCVax #Immunotherapy #BreastCancer #TNBC #HER2 #LeptomeningealDisease #Oncology #Biotech #CNPV #FDA #DoD #CancerResearch #CellTherapy

@teachingquality CLI Showcase 2023 #CLI2023 #efficacydata

If you want to mandate a Vaccine, We need to see the #COVID Vaccine #Efficacydata as it relates to all known #variants. Why is this such a controversial topic?

Dette var visst galt. I følge ledelsen kommer all efficacydata (effekt) - ORR, mPFS, og OS - på børsmelding den 20. mai - abstraktet kommer kl 23 den 19. mai. Fremdeles en ganske god sjanse for 🚀

India has squandered it's trust for the vaccine. Lack of efficacy data has undermined it's trust and without proper testing it will be a foolishness by Indian govt to roll it out to such a large extent. #efficacydata #VaccinePolitics #EmergencyMedicine

We can spend money on a vaccine commission to research a topic with endless saftety/efficacydata but the EPA is a waste of money?#badscience