NWBO: Once In A Decade Best Stock Investment -- Regulatory Approvals Coming! [Dec10, 2022 在第一页加了中文简述]

1717506155907.png
 
8-k filed today: NORTHWEST BIOTHERAPEUTICS INC (Form: 8-K, Received: 06/04/2024 17:11:59)


Item 1.01.Entry into a Material Definitive Agreement.




On June 4, 2024, Northwest Biotherapeutics, Inc. (the “Company”)entered into a Stock Purchase Agreement (SPA) with SIO Capital Management LLC, for SIO's purchase of eight million, one hundred twenty-fivethousand (8,125,000) shares of the Company's common stock at forty cents ($0.40) per share based on certain terms initially negotiatedon May 31, 2024. The transaction is expected to close on June 5, 2024. The gross proceeds will be $3,250,000. The funds will be used forthe Company’s ongoing business operations. Joseph Gunnar & Co., LLC acted as placement agent.
 
Well Les' talk on the big biz show regarding possible HMRA approval, " later, in the fall" now is confirmed:

[7March confirmation + 150 days without RFI + 60 days with RFI]

1718060441333.png
1718060497058.png
 

OTC Markets | Official site of OTCQX, OTCQB and Pink Markets

www.otcmarkets.com www.otcmarkets.com

Northwest Biotherapeutics Announces Exclusive In-License of Portfolio of Dendritic Cell Technology and Intellectual PropertyPress Release | 06/17/2024
Northwest Biotherapeutics Announces Exclusive In-License of Portfolio of Dendritic Cell Technology and Intellectual Property

PR Newswire

BETHESDA, Md., June 17, 2024

Complementary to Technology & IP Already Owned or In-Licensed;
Significant Step in Building a Leading Dendritic Cell Franchise

BETHESDA, Md., June 17, 2024 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today that on June 12, 2024 it entered into an exclusive license from Roswell Park Comprehensive Cancer Center for a portfolio of dendritic cell technologies and intellectual property (IP). The technologies are already in Phase 2 clinical trials, and the Company plans to collaborate with the lead scientist-clinician, Dr. Pawel Kalinski, on the further development of the technologies. The license is the culmination of more than 2 years of discussions and negotiations.

Northwest Biotherapeutics Logo. (PRNewsFoto/Northwest Biotherapeutics, Inc.)

The license includes 5 new patent families that were just filed in 2023 and hence have their full potential patent life ahead of them. The technologies include enhanced versions of dendritic cells (DCs) and DC based therapies, as well as conditioning regimens designed to enhance patient responses and approaches to reprogram the tumor microenvironment to boost immune therapies and help overcome resistance to checkpoint inhibitors.

The DC based therapies include versions with tumor antigens loaded into the DCs and versions for intra-tumoral administration without pre-loading of antigens. Phase 2 trials involving the licensed technologies for two different cancers opened for enrollment earlier this year and are currently under way, and a third Phase 2 trial for a third cancer is pending. The trials are fully funded by grant funding and are being conducted as investigator led trials. The Company does not anticipate having to provide any funding or undertake any operational role for these trials.

As previously reported, over time the Company has been quietly in-licensing various technologies and IP from various institutions and entities which it believes can be valuable in building a leading franchise in dendritic cell therapies.

The portfolio in-licensed from Roswell Park is complementary to, and builds upon, a portfolio which the Company exclusively licensed from another institution last year. Together, the two portfolios encompass more than 20 years of work by one of the foremost groups of dendritic cell experts, led by Dr. Kalinski.

The portfolio in-licensed last year includes the foundational technologies and IP, and positive early-stage clinical trial results, developed by the Kalinski group over 17 years before coming to Roswell. The portfolio in-licensed now includes the further work during the last 7 years at Roswell. Taken together, the Company believes that the two portfolios comprise a whole that is greater than the sum of its parts and offer compelling synergies with the Company's own portfolio. The Company plans to collaborate with Dr. Kalinski on the further clinical development of the combined technologies.

The Company believes that the infrastructure and systems it has developed, and experience it has gained, in producing and delivering personalized living-cell DC based therapies for large numbers of patients make it uniquely positioned to help accelerate the late-stage development of the licensed DC technologies. The Company's 331-patient Phase 3 clinical trial remains one of the largest personalized cell therapy trials conducted to date, and the Company's extensive experience treating compassionate use patients has added valuable ongoing "real world" experience.

"We are excited to join forces with Dr. Kalinski, one of the foremost experts on dendritic cell biology and therapies," commented Linda Powers, the Company's CEO. "We also greatly appreciate the supportiveness of the institutions throughout the long process of working out the arrangements to keep the Kalinski portfolios intact and to license them to NWBio. In the immediate term, we will continue to focus intensively on pursuing the approval and commercialization of DCVax®-L for glioblastoma, but we are excited to begin working on growth opportunities with the licensed technologies as well."

The terms of the Roswell license include standard provisions for an upfront license fee and milestones related to the first Phase 2 trial, first Phase 3 trial, first product approval and first commercial sale. If all of the milestones are met, the payments would be approximately $2.3 million. The license terms also include royalties of 4% on product sales (potentially reduced to 3% in the event of royalty stacking).

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products that are designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis. The Company has a broad platform technology for DCVax® dendritic cell-based vaccines. The Company's lead program involves DCVax®-L treatment for glioblastoma (GBM). GBM is the most aggressive and lethal form of primary brain cancer, and is an "orphan disease." The Company has completed a 331-patient Phase III trial of DCVax-L for GBM, presented the results in scientific meetings, published the results in JAMA Oncology and submitted a MAA for commercial approval in the UK. The Company has also developed DCVax®-Direct for inoperable solid tumor cancers. It has completed a 40-patient Phase I trial and, as resources permit, plans to pursue Phase II trials. The Company previously conducted a Phase I/II trial with DCVax-L for advanced ovarian cancer together with the University of Pennsylvania.

Disclaimer

Statements made in this news release that are not historical facts, including statements concerning plans for DCVax are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "expect," "believe," "intend," "design," "plan," "continue," "may," "will," "anticipate," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those projected in any forward-looking statement. Readers should not rely upon forward-looking statements. There are a number of important factors that could cause actual results to differ materially from those anticipated, including, without limitation, risks related to delays or uncertainties in regulatory processes and decisions, risks related to the Company's ability to achieve timely performance of third parties, risks related to whether the Company's products, including products involving in-licensed intellectual property, will be viewed as demonstrating safety and efficacy, risks relating to funding or implementation of clinical trials, including trials involving in-licensed intellectual property, risks related to the Company's ongoing ability to raise additional capital, and other risks included in the Company's Securities and Exchange Commission ("SEC") filings. Additional information on the foregoing risk factors and other factors, including Risk Factors, which could affect the Company's results, is included in its SEC filings. Finally, there may be other factors not mentioned above or included in the Company's SEC filings that may cause actual plans, results or timelines to differ materially from those projected in any forward-looking statement. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.

CONTACTS

Northwest Biotherapeutics

Dave Innes
804-513-6758
dinnes@nwbio.com

Les Goldman
240-234-0059
lgoldman@nwbio.com

Cision View original content to download multimedia:Northwest Biotherapeutics Announces Exclusive In-License of Portfolio of Dendritic Cell Technology and Intellectual Property

SOURCE Northwest Biotherapeutics
 
[out of topic]

bought some VRNA for a quick gain or loss. VRNA has a FDA PDUFA day of tomorrow, 26 June 2024. if approved, I will sell and if not I will sell for a loss.

Pros:
- Good, but not Earth-shattering results in P3
- New MOA
- Complementary to other therapies
- Very little innovation in the last decade or two
- Safer alternative to Rofluminast (I think ~33m sales in
2023.) Gives prescribers something to give to patients
responding to that drug that has fewer side effects
and additionally inhibits PDE4
- Safer anti-inflammatory than OCS (FDA may not give
this much weight because studies didn't look at this
but FDA may give it some consideration.)
Cons:
- SOC changed a bit after the trials were designed.
- Improvements on QOL were mixed.
- Dropout rate in P3 (Covid.)
 
最后编辑:
Northwest Biotherapeutics Announces Positive Votes At Annual Meeting; Reviews Strong Progress and Growth OpportunitiesPress Release | 07/03/2024
Northwest Biotherapeutics Announces Positive Votes At Annual Meeting; Reviews Strong Progress and Growth Opportunities

PR Newswire

BETHESDA, Md., July 3, 2024

Over 77% Of All Shares Voted; Proposals Received Overwhelming Positive Votes

BETHESDA, Md., July 3, 2024 /PRNewswire/ -- Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, reported positive results of voting at the Annual Shareholders Meeting on June 29, 2024.

Northwest Biotherapeutics Logo. (PRNewsFoto/Northwest Biotherapeutics, Inc.)

Annual Meeting Results

There was an exceptionally strong vote turnout at the 2023 Annual Meeting, with 961.7 million votes cast out of the total 1.2 billion shares outstanding as of the record date, comprising over 77% of all common and preferred shares outstanding. This vote turnout repeated the exceptional turnout at the 2022 Annual Meeting, where 841 million votes were cast comprising 78% of the total shares that were then outstanding.

There were 5 Proposals for shareholders to decide at the 2023 Annual Meeting, and all of them were approved by shareholders with overwhelming margins. The votes were as follows:

Proposal 1: Re-Election of Class I Directors for a new 3-year term

Dr. Alton Boynton was re-elected. 94.04% of the votes cast were in favor.
Ambassador Cofer Black was re-elected. 93.01% of the votes cast were in favor.

Proposal 2: Ratification of Appointment of Independent Auditor – Cherry Bekaert

The appointment was ratified. 92.73% of the votes cast were in favor.

Proposal 3: Ratification of Stock Options awarded to Management in 2020.

The Option awards were ratified. 88.13% of the votes cast were in favor.

Proposal 4: Ratification of Stock Options Awarded to Non-Executive Directors in 2020.

The Option awards were ratified. 88.05% of the votes cast were in favor.

Proposal 5: Approval, on an advisory basis, of executive compensation in 2023.

The compensation was approved on an advisory basis. 87.37% of the votes cast were in favor.

Review of Progress Since Prior Annual Meeting, and Plans and Opportunities Going Forward

During the Annual Meeting, the Company also conducted an informal discussion session that was publicly available by audio link to all interested parties. An audio recording has also been posted on the Company's website and will remain available there through Sunday, July 7, 2024.

During the discussion session, the Company reviewed its strong progress since the last Annual Meeting and described its plans and priorities, and its many growth opportunities, going forward. The Company's descriptions of plans and opportunities were subject to standard cautions about forward looking statements and related uncertainties and risks.

"We are excited about the Company's progress on many fronts over the last 18 months, including in regard to the Marketing Authorization Application (MAA) in the UK, the Sawston facility, the Flaskworks system, the Company's intellectual property portfolio and collaborations, the Company's lawsuit against parties whom the Company believes have been manipulating the Company's stock, and other matters," commented Linda Powers, the Company's CEO.

"We are especially grateful for the ongoing strong support from our shareholders, as reflected in the exceptional voting results of the Annual Meeting."

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products that are designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis. The Company has a broad platform technology for DCVax® dendritic cell-based vaccines. The Company's lead program involves DCVax®-L treatment for glioblastoma (GBM). GBM is the most aggressive and lethal form of primary brain cancer, and is an "orphan disease." The Company has completed a 331-patient Phase III trial of DCVax-L for GBM, presented the results in scientific meetings, published the results in JAMA Oncology and submitted a MAA for commercial approval in the UK. The Company has also developed DCVax®-Direct for inoperable solid tumor cancers. It has completed a 40-patient Phase I trial and, as resources permit, plans to pursue Phase II trials. The Company previously conducted a Phase I/II trial with DCVax-L for advanced ovarian cancer together with the University of Pennsylvania.

Disclaimer

Statements made in this news release that are not historical facts, including statements concerning plans for DCVax are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "expect," "believe," "intend," "design," "plan," "continue," "may," "will," "anticipate," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those projected in any forward-looking statement. Readers should not rely upon forward-looking statements. There are a number of important factors that could cause actual results to differ materially from those anticipated, including, without limitation, risks related to delays or uncertainties in regulatory processes and decisions, risks related to the Company's ability to achieve timely performance of third parties, risks related to whether the Company's products, including products involving in-licensed intellectual property, will be viewed as demonstrating safety and efficacy, risks relating to funding or implementation of clinical trials, including trials involving in-licensed intellectual property, risks related to the Company's ongoing ability to raise additional capital, and other risks included in the Company's Securities and Exchange Commission ("SEC") filings. Additional information on the foregoing risk factors and other factors, including Risk Factors, which could affect the Company's results, is included in its SEC filings. Finally, there may be other factors not mentioned above or included in the Company's SEC filings that may cause actual plans, results or timelines to differ materially from those projected in any forward-looking statement. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.

CONTACTS




Northwest Biotherapeutics




Dave Innes


Les Goldman

804-513-6758


240-234-0059

dinnes@nwbio.com


lgoldman@nwbio.com



Cision View original content to download multimedia:Northwest Biotherapeutics Announces Positive Votes At Annual Meeting; Reviews Strong Progress and Growth Opportunities

SOURCE Northwest Biotherapeutics
 
thejns.org

Tumor regression following autologous tumor lysate–loaded dendritic cell vaccination immunotherapy: illustrative case

BACKGROUND Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate–loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a...
thejns.org thejns.org

Tumor regression following autologous tumor lysate–loaded dendritic cell vaccination immunotherapy: illustrative case
Ahmad I Kamaludin MBBCh BAO, MCh, Naomi Sibtain MBBS and Keyoumars Ashkan MBBCh, MD, DSc
View Less

DOI link:
https://doi.org/10.3171/CASE24112

Publication Date:
08 Jul 2024

Open access

Download PDF

ABSTRACT
Full Text
PDF

BACKGROUND

Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate–loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial.
OBSERVATIONS

A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality.
LESSONS

The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease.

thejns.org

Tumor regression following autologous tumor lysate–loaded dendritic cell vaccination immunotherapy: illustrative case

BACKGROUND Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate–loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a...
thejns.org thejns.org

Keywords:
tumor regression; glioblastoma; DCVax-L; immunotherapy; treatment; case report

ABBREVIATIONS
CNS = central nervous system DCVax-L = autologous tumor lysate-loaded dendritic cell vaccination GBM = glioblastoma multiforme IDH = isocitrate dehydrogenase MRI = magnetic resonance imaging SOC = standard of care WHO = World Health Organization

Glioblastoma multiforme (GBM) is the most common malignant primary central nervous system (CNS) tumor, accounting for 16% of all primary CNS tumors and 54% of all gliomas.1 GBM is highly aggressive, with a median survival of 15–17 months and a 5-year survival rate of 5%.2 Despite decades of research into therapeutic options for GBM, recurrence rates continue to be dismally high at 90%, with the tumor typically recurring within 6–8 months.3 GBMs with certain molecular markers, such as O6-methylguanine-DNA-methyltransferase methylation or isocitrate dehydrogenase (IDH) mutation, are known to confer a slightly more favorable prognosis, with the presence of the latter now referred to as “IDH-mutant grade 4 astrocytoma” in the 5th edition update of the World Health Organization (WHO) classification of CNS tumors.4

The standard of care (SOC) treatment for grade 4 gliomas, in general, is gross-total resection, postoperative radiotherapy to 60 Gy in 30 fractions with concomitant temozolomide, followed by adjuvant temozolomide chemotherapy.5 This has remained virtually unchanged for almost 2 decades because of the lack of novel treatment options.6, 7 An important emerging therapeutic approach for these tumors includes the use of immunotherapy, whereby autologous tumor lysate–loaded dendritic cell vaccination (DCVax-L), in particular, has shown significant promise.8 Here, we report the case of a patient who underwent DCVax-L treatment at our center.
Illustrative Case

A 34-year-old male, previously fit and well, presented to his general practitioner with multiple episodes of transient lightheadedness, dizziness, and headaches over a 4-month period. He experienced up to 4 episodes daily, which impacted his work and day-to-day activities. His neurological examination at presentation revealed no focal deficits.

He underwent magnetic resonance imaging (MRI) of his brain, which revealed a large heterogeneous enhancing lesion in the right frontotemporal and insular region likely to be a high-grade tumor (Fig. 1). Imaging of his chest, abdomen, and pelvis revealed nothing of note. He was started on dexamethasone and levetiracetam, and a week later, he underwent an asleep right temporoparietal craniotomy for debulking of the right temporal lobe component of the tumor. Postoperative imaging showed residual tumor primarily in the frontal lobe and amygdala (Fig. 2). His postoperative course was uneventful. Histopathology demonstrated a methylated, IDH-mutant astrocytoma (CNS WHO grade 4).
FIG. 1.
FIG. 1.

Axial T2-weighted (A and B) and axial T1-weighted post-gadolinium (C) images show an area of mixed T2 hyperintensity and isointensity with heterogeneous enhancement in the right fronto-insulo-temporal region, corresponding to a high-grade glioma.
FIG. 2.
FIG. 2.

Axial T2-weighted images (A and B) show a resection cavity (black arrows) at the site of the previously shown temporal component of the astrocytoma. Residual tumor is evident mainly in the frontal lobe and amygdala (white arrows).

Postoperatively, he received SOC treatment with concomitant radiotherapy and temozolomide, followed by 6 cycles of adjuvant temozolomide (Stupp protocol). He tolerated the chemoradiotherapy well with only fatigue as his primary complaint. He received 3 doses of DCVax-L, on a compassionate basis, as part of his oncological treatment, administered in 3 consecutive weekly doses. There were no other conventional treatments, although he did use a range of off-label medications and daily supplements (Table 1). He continued with surveillance MRI. After 3 cycles of temozolomide, MRI showed a non-enhancing cyst–like area in the right frontal lobe where residual tumor had been noted previously (Fig. 1A), while the residual tumor component in the amygdala had regressed entirely (Fig. 3B). At 1 year postoperatively, the cystic area had further reduced in size since the previous study with no evidence of recurrence (Fig. 4). The patient reported that he was clinically well and had since returned to preoperative functionality and worked at a full-time capacity.
FIG. 3.
FIG. 3.

Axial T2-weighted (A) and T1-weighted post-gadolinium (B) images show a well-defined, homogeneous signal, a non-enhancing cyst–like area in the right frontal lobe anterior to the temporal resection cavity, at the site of the previously shown area of residual tumor (white arrows). Axial T2-weighted image more inferiorly (C) the previously shown residual tumor component in the amygdala medial to the resection cavity is also no longer evident (black arrow).
FIG. 4.
FIG. 4.

Axial T2-weighted (A) and T1 post-gadolinium (B) images show a reduction in the size of the well-defined, non-enhancing cystic area in the right frontal lobe (arrows) since the previous study. Axial fluid–attenuated inversion recovery image (C) demonstrates signal suppression of the contents of this area (arrow), confirming its cystic nature. There remains no evidence of tumor recurrence.
TABLE 1.

List of off-label medications and supplements
Medications Supplements & Other Treatments
Metformin Probiotics Curcumin Quercetin
Atorvastatin Vitamin B Indole-3-carbinol Feverfew
Mebendazole Milk thistle EGCG Pau d’arco
Etodolac Garlic & oregano Omega 3 Mistletoe IM
Cimetidine Papaya leaf Hydroxychloroquine Vitamin C IV
Melatonin Vitamin D Turkey tail fungi Artemisinin IV
Valaciclovir Boswellia Bromelain Helleborus IV
Niclosamide Magnesium Broccoli extract Curcumin IV
Zinc Red clover Hyperbaric oxygen
Lycopene Berberine

EGCG = epigallocatechin gallate; IV = intravenous; IM = intramuscular.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.
Discussion
Observations

GBM, depending on the IDH mutation status, could be classified into either IDH-wildtype or IDH-mutant GBM.9 Reflecting the current increased understanding of the importance of IDH mutation in the pathogenesis and subsequent prognosis of gliomas, GBMs that are IDHmutant are now referred to as IDH-mutant grade 4 astrocytomas since the 2021 update of the WHO classification of CNS tumors.4, 10 Despite slightly more favorable disease outcomes as compared to those for IDH-wildtype GBMs, IDH-mutant grade 4 astrocytomas are still considered malignant, incurable tumors with aggressive behavior and a median survival of around 30 months.10 IDH-mutant GBM or grade 4 astrocytoma is more prevalent in the younger cohort than the IDH-wildtype GBM (median age 45 vs 62 years), as exemplified by our patient, and is thought to result from secondary transformation of lower-grade astrocytomas.11, 12

Developing an effective treatment for GBM is extremely challenging for a multitude of reasons, one of which is attributed to its inherent heterogeneity, either intratumorally or intertumorally.13 Large-scale genomic profiling has demonstrated enormous variability for genetic expression and subtypes across the patient population.14 In addition, molecular heterogeneity within the tumor itself also poses a challenge because of differing properties and levels of resistance to therapeutic approaches. This has been postulated to contribute to the innate resistance of GBMs to current treatments designed to target specific tumor characteristics, which only eliminate a fraction of tumor cells and eventually fail due to relapse of the remaining unaffected tumor.15

The Stupp protocol, which is the current SOC treatment, evaluated the addition of concomitant temozolomide during radiotherapy followed by 6 cycles of adjuvant temozolomide.5 Stupp et al. demonstrated an increase in median survival by 2.5 months (12.1 vs 14.6 months) and an improved 2-year survival rate (26.5% vs 10.4%) when compared to radiotherapy alone. Since the publication of the protocol in 2005, there have been no further phase 3 clinical trials for systemic treatments that have demonstrated a significant survival benefit for patients with GBM.6, 7 An exception to this is DCVax-L, where the findings of the phase 3 trial revealed, as compared to external controls, an increased median survival of 2.8 months (19.3 vs 16.5 months) in the overall cohort and 9 months (30.2 vs 21.3 months) in methylated GBMs. The 5-year survival rate more than doubled at 13.7% versus 5% in the external control group.

DCVax-L is a novel immunotherapy treatment that utilizes a patient’s own tumor combined with dendritic cells to mobilize an antitumor response.8 Since the patient’s own tumor lysate is used to prime the dendritic cells, this addresses the aforementioned heterogeneity of GBMs, making it possible to target the spectrum of antigens present in a patient’s tumor. This can also prevent mutational processes from occurring around targeted antigens when only a few antigens are targeted.16 In addition, using dendritic cells as the antigen delivery vehicle versus other agents can bring about a broader immune response, including vastly diverse T-cell populations.17 Herein, we report a patient with an IDH-mutant grade 4 astrocytoma who received DCVax-L treatment alongside SOC therapy and subsequently demonstrated significant tumor regression together with a return to preoperative functionality and quality of life. The radiological regression remained stable 1 year after surgery with no evidence of recurrence. The limitation of our report is that the observation is related to a single patient; therefore, it is not possible to establish an absolute causality and generalizability with DCVax-L. The patient also reported taking multiple off-label medications and supplements, which may have played a contributory role in the regression, although such treatments lack any concrete class I evidence for use in glioma patients.
Lessons

We report a patient who demonstrated significant radiological regression of his residual tumor following the administration of SOC adjuvant chemoradiotherapy (Stupp protocol) alongside a course of DCVax-L treatment. The pattern and extent of tumor regression are highly unusual and atypical of what is seen with adjuvant SOC treatment alone, even in IDH-mutant gliomas. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease.
Disclosures

Dr. Kamaludin reported an educational grant from Northwest Biotherapeutics outside the submitted work. Dr. Ashkan reported grants from Northwest Biotherapeutics outside the submitted work.
Author Contributions

Conception and design: Kamaludin, Ashkan. Acquisition of data: Kamaludin, Ashkan. Analysis and interpretation of data: all authors. Drafting the article: Kamaludin, Sibtain. Critically revising the article: Kamaludin, Ashkan. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Kamaludin. Statistical analysis: Kamaludin. Administrative/technical/material support: Kamaludin, Ashkan. Study supervision: Ashkan.
Supplemental Information
Previous Presentations

This work has been presented as a poster presentation at the Society of British Neurological Surgeons Spring Meeting, April 16–19, 2024, Edinburgh, United Kingdom.
Correspondence

Ahmad I. Kamaludin: King’s College Hospital, London, United Kingdom. ahmad.kamaludin@nhs.net.
References

1.↑

Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15(suppl 2):ii1-i i 56.
PubMed
Search Google Scholar
Export Citation
2.↑

Poon MTC, Sudlow CLM, Figueroa JD, Brennan PM. Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis. Sci Rep. 2020;10(1):11622.
PubMed
Search Google Scholar
Export Citation
3.↑

Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro-Oncology. 2013;15(1):4-27.
PubMed
Search Google Scholar
Export Citation
4.↑

Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
PubMed
Search Google Scholar
Export Citation
5.↑

Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996.
PubMed
Search Google Scholar
Export Citation
6.↑

Bagley SJ, Kothari S, Rahman R, et al. Glioblastoma clinical trials: current landscape and opportunities for improvement. Clin Cancer Res. 2022;28(4):594-602.
PubMed
Search Google Scholar
Export Citation
7.↑

Vanderbeek AM, Rahman R, Fell G, et al. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Neuro Oncol. 2018;20(8):1034-1043.
PubMed
Search Google Scholar
Export Citation
8.↑

Liau LM, Ashkan K, Brem S, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncol. 2023;9(1):112-121.
PubMed
Search Google Scholar
Export Citation
9.↑

Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803-820.
PubMed
Search Google Scholar
Export Citation
10.↑

Han S, Liu Y, Cai SJ, et al. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020;122(11):1580-1589.
PubMed
Search Google Scholar
Export Citation
11.↑

Barresi V, Simbolo M, M

afficini A, et al. Ultra-mutation in IDH wild-type glioblastomas of patients younger than 55 years is associated with defective mismatch repair, microsatellite instability, and giant cell enrichment. Cancers (Basel). 2019;11(9):1279.
PubMed
Search Google Scholar
Export Citation
12.↑

Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep. 2013;13(5):345.
PubMed
Search Google Scholar
Export Citation
13.↑

Lam KHB, Valkanas K, Djuric U, Diamandis P. Unifying models of glioblastoma’s intratumoral heterogeneity. Neurooncol Adv. 2020;2(1):vdaa096.
PubMed
Search Google Scholar
Export Citation
14.↑

Verhaak RGW, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110.
PubMed
Search Google Scholar
Export Citation
15.↑

Bergmann N, Delbridge C, Gempt J, et al. The intratumoral heterogeneity reflects the intertumoral subtypes of glioblastoma multiforme: a regional immunohistochemistry analysis. Front Oncol. 2020;10:494.
PubMed
Search Google Scholar
Export Citation
16.↑

Wen PY, Reardon DA, Armstrong TS, et al. A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma. Clin Cancer Res. 2019;25(19):5799-5807.
PubMed
Search Google Scholar
Export Citation
17.↑

Whiteside TL. Immune responses to malignancies. J Allergy Clin Immunol. 2010;125(2 suppl 2):S272-S283.
PubMed
Search Google Scholar
Export Citation

Cover Journal of Neurosurgery: Case Lessons
Volume 8 (2024): Issue 2 (Jul 2024)
in Journal of Neurosurgery: Case Lessons
Search within Journal...
Issue Journal
Volume 8: Issue 2

eTOC Alerts

Article has an altmetric score of 21
Contributor Notes
Correspondence Ahmad I. Kamaludin: King’s College Hospital, London, United Kingdom. ahmad.kamaludin@nhs.net.

INCLUDE WHEN CITING Published July 8, 2024; DOI: 10.3171/CASE24112.

Disclosures Dr. Kamaludin reported an educational grant from Northwest Biotherapeutics outside the submitted work. Dr. Ashkan reported grants from Northwest Biotherapeutics outside the submitted work.

Keywords:
tumor regression; glioblastoma; DCVax-L; immunotherapy; treatment; case report
 
[out of topic]

1. sold a bit earlier for less profit

1720800204573.png

2. Initiate a new position

1720800254820.png
 
您必须登录或注册才可回复。
后退
顶部