Stacey MacArthur

$NWBO #DCVax #DCVaxForBraelyn 𝗦𝗮𝗺𝗲 𝘃𝗮𝗰𝗰𝗶𝗻𝗲. 𝗦𝗮𝗺𝗲 𝗯𝗼𝗼𝘀𝘁𝗲𝗿. 𝗦𝗮𝗺𝗲 𝗞𝗲𝘆𝘁𝗿𝘂𝗱𝗮. 𝗢𝗻𝗹𝘆 𝘁𝗵𝗲 𝗼𝗿𝗱𝗲𝗿 𝗰𝗵𝗮𝗻𝗴𝗲𝗱. Vaccine first: 555 days. #Keytruda first: 271 days. Once #glioblastoma comes back, patients live six to ten months. The Keytruda-first arm, at 8.9 months, landed right where this disease always lands. Vaccine first: 18.2 months. Nothing close has been reported in a randomized trial of recurrent glioblastoma. A 2021 Cochrane review of the trials at first recurrence found medians between 5.5 and 12.6 months. The few higher numbers anywhere come from single-arm or retrospective studies that choose their own patients. This one was randomized. The reason fits in three lines. Keytruda takes the brakes off the immune system's killers. The vaccine teaches them what to kill. Teach first, then release. 𝗧𝗵𝗲 𝗱𝗲𝗰𝗶𝘀𝗶𝗼𝗻 𝘁𝗵𝗮𝘁 𝗺𝗮𝗱𝗲 𝗶𝘁 𝗽𝗼𝘀𝘀𝗶𝗯𝗹𝗲 𝘄𝗮𝘀 𝘁𝗮𝗸𝗲𝗻 𝗶𝗻 𝟮𝟬𝟬𝟮, 𝗯𝘆 𝘁𝘄𝗼 𝗺𝗲𝗻 𝗮𝗹𝗺𝗼𝘀𝘁 𝗻𝗼𝗯𝗼𝗱𝘆 𝘄𝗮𝘀 𝗹𝗶𝘀𝘁𝗲𝗻𝗶𝗻𝗴 𝘁𝗼. 𝗧𝗵𝗲 𝘁𝗿𝗶𝗮𝗹 UCLA reported it for EANO 2026 (NCT04201873): 16 patients randomized to the vaccine first, 19 to Keytruda first, all with the more aggressive, IDH wild-type form. Hazard ratio 0.32. The two groups did not differ significantly in how much tumor surgery left behind, or in mutation load. The booster in both arms is poly-ICLC, sold as Hiltonol. 𝗛𝗼𝘄 𝗶𝘁 𝘄𝗼𝗿𝗸𝘀 Keytruda kills nothing. It takes the brakes off T cells, the immune system's killers. That only helps if the killers already know what to attack. Teaching them is the job of the dendritic cell. It works like a switch. On, in what immunologists call the type-1 state, it gives the order to kill. Off, it goes silent, and a tumor is very good at holding it off. The vaccine is made of the patient's own dendritic cells, grown outside the body where nothing has switched them off, then loaded with the patient's own tumor. It arrives with the switch already on. And it reads the whole tumor, not a target someone chose. In 2008 one dose of this kind of vaccine, loaded with a man's own tumor, found a virus hiding in it that nobody knew was there. The cells found it because they were not looking for anything. Vaccine first, and the cells teach, and then Keytruda releases an army that knows its target. The trial saw it: more T cells inside the tumor, carrying interferon and granzyme B, the enzyme a killer T cell uses to destroy its target. Keytruda first: chronic inflammation instead. 𝗣𝗿𝗼𝗼𝗳 𝗯𝘆 𝗺𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺 The FDA's plausible mechanism pathway, set out by Vinay Prasad and Commissioner Marty Makary in the New England Journal of Medicine, asks five questions. This treatment answers all five. 1. A specific broken link? The dendritic cell's switch, held off by the tumor. 2. A product aimed at it? The patient's own dendritic cells, switched on outside the body. 3. A well-known untreated course? Six to ten months, measured in hundreds of trials. 4. Proof the target was hit? T cells in the tumor carrying interferon and granzyme B. 5. A better clinical course? 555 days against 271. The FDA's guidance adds one more test: the improvement must not come from other treatments or from the disease's natural variability. This trial rules out both. Same treatments in both arms. Randomized, balanced, p below 0.0006. The only thing that changed was whether the instruction came first. That is proof by mechanism. 𝗪𝗵𝗼 𝗯𝘂𝗶𝗹𝘁 𝗶𝘁 The UCLA vaccine is ATL-DC, the academic version of DCVax-L. DCVax-L is Northwest Biotherapeutics', and it was invented by Alton Boynton and Marnix Bosch. Boynton filed on dendritic cells loaded with a patient's own tumor in 1995, three years before he co-founded the company. Bosch joined in 2000 and built the manufacturing. Linda Liau, now chair of neurosurgery at UCLA, led the phase 3. Boynton and Bosch are the named inventors on the patents Northwest holds, and the last two authors on the papers she leads. Between 2002 and 2005 they made three decisions, each against where the field was going: 1. 2002: use the whole tumor, not a chosen target. 2. 2003: add interferon gamma, so the cells come out switched on. 3. 2005: stop the cells halfway and inject them straight into tumors that cannot be removed. The second is what makes the other two safe. The third became DCVax-Direct, for tumors a surgeon cannot remove. Both products carry the whole tumor. DCVax-L loads it in the lab, from the tumor the surgeon took out. DCVax-Direct loads it inside the patient. Wherever there is a tumor, they load the tumor. 𝗪𝗵𝘆 𝗶𝘁 𝗶𝘀 𝘀𝗮𝗳𝗲 In DCVax-L's phase 3, patients were given their own brain tumors back, ground up and loaded onto their own cells. Seven of 331 patients had a serious side effect even possibly related to the vaccine. No autoimmune reactions. 𝗧𝗵𝗲 𝗱𝗿𝘂𝗴𝘀 𝘁𝗵𝗮𝘁 𝗻𝗲𝘃𝗲𝗿 𝗳𝗮𝗶𝗹𝗲𝗱 In 2020 a drug from the same class as Keytruda was tested on its own in recurrent glioblastoma and lost. Six years later the same class sat inside the arm that doubled survival. The drug had not changed. This time the switch was on when it arrived. We may already own many of the treatments we need. We have been giving them with the switch off. 𝗦𝘁𝗶𝗹𝗹 𝘄𝗮𝗶𝘁𝗶𝗻𝗴 DCVax-L's phase 3: 13.0 percent alive at five years against 5.7. DCVax-L has not been turned down by the FDA. It has not been submitted. In the UK, a review meant to take 150 days passed 1,000 in September 2026. Boynton is still chief scientific officer. Bosch is still chief technical officer. 𝗕𝗿𝗮𝗲𝗹𝘆𝗻 Braelyn Hollensbe was sixteen when they found it. She had surgery, and it came back. Surgeons at more than one major center looked at what was left and said no. Linda Liau said yes, and took about ninety percent. Hers is the kind of glioblastoma standard chemotherapy works least well against. Then her family started flying from South Carolina to London for DCVax-L, the vaccine Boynton and Bosch invented and Northwest builds from a patient's own tumor, because it is not licensed where she lives. Three induction doses, then a fourth, fitted around the start of college. Then the Keytruda. In that order. On August 28 a scan went to Liau and the UCLA tumor board. What had been left behind at surgery was not there. On September 15 her mother wrote the sentence she had been waiting to write since Braelyn was sixteen: no evidence of disease. Everything above is an argument about order. For Braelyn it was a schedule. Flip the switch. Then amplify. The video walks through the whole mechanism.