June 12, 2023 By uclahealth 6 min read A personalized vaccine developed by UCLA Health scientists has been shown to potentially extend the life of patients with glioblastoma, the most aggressive form of brain cancer.
As the therapy awaits submission for approval to the U.S. Food and Drug Administration, it is one of the latest examples of UCLA Health research moving from the bench to the bedside.
The results of two other clinical trials at UCLA could also soon provide new therapy options for patients with Alzheimer’s — a disease for which there is no cure and few treatments to manage symptoms. The FDA has granted “accelerated approval” for the amyloid-targeting drug lecanemab, which has been shown to moderately slow cognitive decline.
A similar drug, donanemab, showed promise in a phase 3 study.
“An institution like UCLA offers patients with progressive and ultimately life-ending diseases the opportunity to participate in trials that may benefit them, but the primary goal of any clinical trial is to provide benefit to others,” says S. Thomas Carmichael, MD, PhD, chair of the Department of Neurology at the David Geffen School of Medicine. “When the FDA approves a new therapy, that benefit becomes a reality.”
A vaccine to treat glioblastoma Glioblastoma is the most aggressive primary brain tumor in adults, with more than 10,000 new cases diagnosed in the United States each year. Standard treatment involves surgery, radiation, and chemotherapy; and the median overall survival rate is only 15 to 17 months from diagnosis.
A vaccine to treat glioblastoma called DCVax-L has been in development for several years. Linda Liau, MD, PhD, MBA, and a team of UCLA researchers were the first to investigate whether a patient’s own dendritic cells (a specialized type of immune cell) could be used to create a personalized treatment for the deadly cancer.
“We tested the method with a single patient in 1997, and then moved to a phase 1 safety trial in the early 2000s,” says Dr. Liau, professor and chair of Neurosurgery at UCLA.
A series of phase 2 early efficacy and optimization trials followed, and then an international, multi-site study led by Dr. Liau began in 2007.
The vaccine consists of two components: a patient’s dendritic cells, which are special types of immune cells, and proteins prepared from a patient’s tumor.
To create the vaccine, which is individualized for each patient, medical staff first perform a procedure called leukapheresis, in which a patient’s blood is drawn and their white blood cells are collected. Then, the patient’s tumor is removed and sent to a lab where researchers obtain proteins from the specimen, called tumor lysate. The white blood cells are cultured to differentiate into dendritic cells, and then combined with the tumor lysate to make the vaccine.
Dendritic cells are “antigen-presenting” cells, which means that they are able to process all kinds of foreign invaders in the body and alert the immune system’s T cells to mobilize a broad immune response against those invaders. Glioblastoma is a highly heterogenous disease, meaning there are many different types of cancer cells within a single tumor. Therefore, the dendritic cells — loaded with a patient’s own tumor lysate — allow a patient’s immune system to recognize a wide variety of tumor targets and spur the immune system to respond, according to Dr. Liau.
The phase 3 trial led by Dr. Liau involved 331 study participants at 80 sites around the world from August 2007 to November 2015. During the study, 232 people received standard care and DCVax-L at new diagnosis, while 64 out of 99 people received standard care and a placebo. (Patients in the placebo group received the DCVax-L at recurrence.)
The trial results, published in JAMA Oncology in November 2022, showed that newly diagnosed glioblastoma patients receiving the vaccine had an overall survival of 19.3 months on average, compared to 16.5 months on average among the contemporaneous, matched external control group.
“There is a significant subgroup of patients who lived more than five years, but the challenge is trying to determine which patients it may work for, and for which patients it doesn’t,” Dr. Liau says.
At UCLA, Dr. Liau and other researchers are now testing whether the vaccine would be more effective in combination with a PD-1 checkpoint inhibitor. Checkpoint inhibitors are a type of immunotherapy that work by blocking proteins that stop the immune system from attacking cancer cells. While the vaccine allows T-cells to get inside of the tumor, the checkpoint inhibitors may allow T-cells to be more functional and better attack the tumor cells.
“Because of the heterogeneity of glioblastoma, I don’t think there is going to be one drug or one treatment that is going to be effective for all patients. The future of glioblastoma treatments is going to be these combination approaches,” Dr. Liau says.
Hope for an Alzheimer’s cure The diagnosis of Alzheimer’s disease, which is rapidly increasing in prevalence and incidence worldwide, can lead to a sense of “hopelessness” among patients, their caregivers, and their doctors, says Dr. Carmichael.
More than 6 million Americans have the disease — the sixth leading cause of death in the United States.
“There is even a sense of nihilism in doctors, who think, ‘Well, if a patient has memory loss, why even test them for Alzheimer’s?’ Because whether they have the disease or another kind of dementia, we can’t do much to help them.”
Following years of failed — and some controversial — trials for Alzheimer’s therapies, one drug will soon be available to patients, with another on its way.
The treatment lecanemab was granted accelerated approval by the FDA in January of this year. The drug, sold under the brand name Leqembi, is made by the pharmaceutical company Eisai in partnership with Biogen, and is delivered to patients by an intravenous infusion every two weeks.
The drug targets the sticky, abnormal protein amyloid, which builds up in the brain and is a hallmark of Alzheimer’s. Participants who received lecanemab in the phase 3 clinical trial showed a significant reduction in amyloid in imaging tests. However, the reduction in amyloid did not necessarily translate to dramatic cognitive improvement. The results from the multi-site clinical trial were published in the New England Journal of Medicine.
Lecanemab also comes with a high price tag, and access to the drug will depend on whether it receives traditional FDA approval and could be covered by Medicare.
Lilly has applied for FDA approval of its Alzheimer’s drug, donanemab, which similarly targets amyloid. Results from its phase 3 trial have not been peer-reviewed, but a press release from the pharmaceutical company said that nearly half of participants had no clinical progression after one year.
“What’s been surprising, and a bit disappointing, is that these drugs didn’t have as dramatic an effect on cognitive recovery or cognitive decline,” Dr. Carmichael says. “They had a very, very — that’s two ‘verys’ — modest effect on cognition.”
Still, even a modest effect on cognition is notable for patients living with an incurable, degenerative disease, Dr. Carmichael says. And, most importantly, it opens the idea that Alzheimer’s is indeed treatable.
“The scientific community has essentially finished with amyloid — we’ve identified it, developed drugs, and can clear it,” Dr. Carmichael says. “The fact that clearing amyloid doesn’t substantially change the progression of the disease means that other things are also going on in the brains of Alzheimer’s disease patients.”
At UCLA, researchers are investigating, for example, how inflammation may impact Alzheimer’s disease progression, as well as the role of the protein tau.
“There are a lot of interesting questions,” Dr. Carmichael says, “that now are even more important to answer.”
Lauren Ingeno is the author of this article.
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Pipette and test tubes View All News & Insights Tags CancerResearchScience & Research Related Services NeurologyNeurosurgeryUCLA NeurologyUCLA Neurosurgery Related Providers Tom Carmichael Jr., MD, PhD Tom Carmichael Jr., MD, PhD Neurorehabilitation, Neurology Linda Liau, MD, MBA Linda M. Liau, MD, PhD, MBA Brain and Tumor Neurosurgery, Neurosurgery Share:
OncoJock: In answer to your IHUB post 600347(see at bottom) ,the 10 biggest cancer therapy players and checkpoint inhibitor manufacturers do not need a peer reviewed journal to tell them what strategic moves they need to attempt after DC VAX L gets MAA approval (8/1/23?). The quotes below reflect recent conversations about DC VAX L relative to thinkers at those companies .
1) "Au contraire, when the MIA was awarded on 3/20/23, the train left the station. That predestined MAA approval , which should arrive about 8/1/23. Everybody knew that the MAA award would precipitate 2 partnerships , and bids for NWBO by 5 of the biggest CI players. Net, net, NWBO change of control 30 days after the MAA award. But the Bosch MOA Bomb on 6/3/23 increases the bids to 10 within 30 days of the MAA award.Why? Because the big boys know the MOA Bosch described will revolutionize medicine. And it is moated by patents, proprietary manufacturing technology, and knowhow."
2) "So bottom line, DCVax-L Cell Based Platform Technology is a developed process that allows medical science to Direct The Immune System in a general application for all diseases. It improves all existing treatments used in healthcare as we know it!!!In very simple terms, it is the APPLE of modern healthcare treatments!!!Cheers,BBBright BoyRe: Lykiri post# 600189Saturday, June 10, 2023 10:48:29 AMPost# of 600341"
3) Prior to Marnix Bosch's ( CTO-NWBO) 6/3/23 ASCO presentation(lecture and slides) AVC (alphavestcapital.com) pointed out that the LIAU-UCLA-SPORE combination trial data showed that all CIs (checkpoint inhibitors) are more efficacious when dosed in combination with DCVax-L, and that some CIs do not work at all without DC VAX L. MRK's Keytruda( a CI with $21 billion in '22 revenues) is a good example. Keytruda as a mono therapy proved in five clinical trials that it did not increase efficacy, compared to SOC, in GBM. But when dosed in combination with DC VAX L , there was impressive efficacy .https://trp.cancer.gov/spores/abstracts/ucla_brain.htmBut on 6/3/23 at ASCO, Marnix Bosch presented data showing that DC VAX L is a process that can direct the immune system response to targets in all diseases, not just all solid tumor cancers. From conversations with our associates in Big Biotech and Pharma , they are shocked because they do not know how to do what NWBO has done .They know their portfolio of drugs will perform better when dosed with DC VAX L . Their attempts to replicate the manufacturing of DC VAX L have come up short . Plus they do not know how to get around the patent moat. They are left with attempting to buy NWBO, or invest in partnerships which will license them the rights to have access to the DC VAX L technology. What strategic moves are afoot ?"
3) Dr. Bosch: " If you use a lysate from another tumor you get new antigens that are more appropriate to that particular tumor.“AGNOSTIC= "A type of therapy that uses drugs or other substances to treat cancer based on the cancer’s genetic and molecular features without regard to the cancer type or where the cancer started in the body. Tissue-agnostic therapy uses the same drug to treat all cancer types that have the genetic mutation (change) or biomarker that is targeted by the drug. It is a type of targeted therapy. Also called tumor-agnostic therapy."
4) Dr. Bosch: 'If you use a lysate from another tumor you get new antigens that are more appropriate to that particular tumor.“
5) AGNOSTIC= "A type of therapy that uses drugs or other substances to treat cancer based on the cancer’s genetic and molecular features without regard to the cancer type or where the cancer started in the body. Tissue-agnostic therapy uses the same drug to treat all cancer types that have the genetic mutation (change) or biomarker that is targeted by the drug. It is a type of targeted therapy. Also called tumor-agnostic therapy." https://www.fda.gov/media/162346/download
6) ATL:"This MOA is not just specific to the brain, but should work for every organ in the human body."
7) "So I'm going to go out on a limb here in my following comments, but I believe it's time and I believe the scientific/medical community is beginning to recognize that Northwest and it's brilliant team from Alton Boynton, Linda Powers, Dr. Bosch, Allen Turner( former NWBO employee), Dr. Linda Liau and her UCLA team, my friend that is truly a legend in the biotech world and everyone else involved in the development, discovery and understanding of the technology that drives the process that is DCVax-L , has provided the world of medicine with the ability to DIRECT THE IMMUNE SYSTEM and thereby TARGET ALL DISEASES!!!!! In simple terms, DCVax-L is able to identify antigens, which in a perfect system, ARE NOT SUPPOSED TO BE THERE !!!! AND GET RID OF THEM!!!!!!! AND Yes!!! You already know what this means !!! DCVax-L represents the platform technology that is a general application for all diseases !!!!! Cheers, BB"
ZIVIC: "Jun 4 1/2 $NWBO Dr. Bosch’s presentation was a quiet K-Boom! In my opinion regarding T cell recruitment, activation, etc. But in particular one needs to comprehend T cell exhaustion in Cancers and in chronic viral infections (age and kill us). The clonal expansion found with DCVax Gregory Zivic, MD @metacollectiveG · Jun 4 $NWBO The “newly expanded” T cell clones I find particularly interesting. T Cell dysfunction and exhaustion cannot be overcome by PD-1 inhibition or Car-T (Car T cells themselves become exhausted and why this therapy has it’s drawbacks) Gregory Zivic, MD @metacollectiveG · Jun 4 2/2 $NWBO Also important was the finding that other Cancer antigens not previously found in GBM were found in the DCs after pulsing with Lysate. Also, viral antigens present. None of these have formally been found on GBM tumors before. Gregory Zivic, MD @metacollectiveG · Jun 4 $NWBO If anyone’s incapable of comprehending this take away one thing; what’s being shown here is the pivot toward how ALL disease will be treated and cured; all solid tumors, blood cancers, autoimmunity, viruses… incredible. Brilliance. https://nwbio.com/wp-content/uploads/NWBT_ASCO_slides_06032022_FINAL.pdfIn "
Re: CrashOverride post# 600284
Saturday, June 10, 2023 5:11:26 PM
Post# 600347 of 600397 Agreed.
So let me re-phrase what I wrote.
I will become more excited about these MOA data after they have been published in a peer-reviewed journal. Until then, the scientific information contained in this slide deck by Dr. Bosch remains of a highly technical and sophisticated but ultimately promotional nature, and it therefore lacks the credibility of other (peer-reviewed) data released at ASCO.
Or . . . . did I miss the part in his talk where he tells us these data have been, or will be, submitted for publication?
NWBO Northwest Biotherapeutics Inc (QB) 0.654 -0.046 (-6.57%) Volume: 1,763,662 Day Range: 0.649935 - 0.6975 Bid: 0.64 Ask: 0.655 Last Trade Time: 3:58:08 PM EDT Total Trades: 575 1D 1M 3M 6M 1Y 5Y Chart for Northwest Biotherapeutics Inc (QB) NWBO Detailed Quote Recent NWBO News Statement of Changes in Beneficial Ownership (4) • Edgar (US Regulatory) • 04/05/2023 11:32:06 PM Statement of Changes in Beneficial Ownership (4) • Edgar (US Regulatory) • 04/05/2023 01:31:24 PM Nightfood, Inc. (OTCQB: NGTF) now in Sonesta International Hotels Multiple Brands • InvestorsHub NewsWire • 03/13/2023 11:35:55 AM Annual Report (10-k) • Edgar (US Regulatory) • 02/28/2023 09:31:58 PM Annual Statement of Changes in Beneficial Ownership (5) • Edgar (US Regulatory) • 02/07/2023 10:55:54 PM Current Report Filing (8-k) • Edgar (US Regulatory) • 01/13/2023 09:34:51 PM Current Report Filing (8-k) • Edgar (US Regulatory) • 01/06/2023 09:42:13 PM Additional Proxy Soliciting Materials (definitive) (defa14a) • Edgar (US Regulatory) • 12/23/2022 10:24:51 PM Additional Proxy Soliciting Materials (definitive) (defa14a) • Edgar (US Regulatory) • 12/16/2022 06:40:40 PM Proxy Statement (definitive) (def 14a) • Edgar (US Regulatory) • 12/05/2022 12:01:37 PM Northwest Bio Accuses Market Makers of Share Price Manipulation • TipRanks • 12/01/2022 03:29:04 PM Proxy Statement - Notice of Shareholders Meeting (preliminary) (pre 14a) • Edgar (US Regulatory) • 11/25/2022 10:30:31 PM Quarterly Report (10-q) • Edgar (US Regulatory) • 11/09/2022 09:31:44 PM Acquisition Completed: Endexx (EDXC)'s HYLA Secures 200k+ Unit Order; 4,500 Puffs per Unit • InvestorsHub NewsWire • 09/27/2022 01:33:31 PM Amended Annual Report (10-k/a) • Edgar (US Regulatory) • 06/30/2022 09:09:33 PM More NWBO News InvestorsHub NewsWire RENNOVA HEALTH, INC. ANNOUNCES THE EXPANSION OF SERVICES AT ITS BIG SOUTH FORK MEDICAL CENTER HOSPITAL, TO INCLUDE SWING BEDS • RNVA • Jun 13, 2023 12:56 PM
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