Latest News

• Novel Radiation Strategy Redefines a New Treatment Paradigm for Glioblastoma        

    This is an interesting approach that makes a lot of sense. After glioblastoma surgery, we usually wait several weeks for the surgical wound to heal before starting radiation and chemotherapy. Unfortunately, glioblastoma does not wait.

   
  GammaTile consists of small absorbable tiles containing radioactive cesium-131 seeds that are placed directly into the tumor cavity at the time of surgery. This allows radiation to begin immediately, targeting residual tumor cells while limiting radiation exposure to the surrounding brain. Patients then go on to receive a shortened course of traditional radiation along with standard chemotherapy.
   
  In this 67-patient Phase I study, only 6% of patients experienced rapid tumor regrowth before beginning the next phase of treatment, compared with historical rates reported as 50–70%. That is certainly encouraging.
   
  However, this was not a randomized trial, so we cannot yet say that GammaTile improves survival or should become the new standard of care for newly diagnosed GBM. A Phase III randomized trial called BRIDGES is now underway to answer that question.
   
  I like the concept. Instead of giving residual glioblastoma cells several weeks to recover and grow after surgery, start attacking them immediately. Now we need the randomized trial to tell us whether that translates into longer survival.

  
  Disclaimer: GT Medical is a proud sponsor of the Musella Foundation!

  
  
• Enrollment opens for Adaptin Bio’s Phase I trial of glioblastoma therapy        

  This is an interesting new approach that is now making the important jump from laboratory studies into its **first human trial**.

   
  Adaptin Bio has opened enrollment at Duke University for a Phase I trial of **APTN-101**, a treatment designed for glioblastomas that express **EGFRvIII**. APTN-101 is what the company calls a Brain Bispecific T-cell Engager, or **BRiTE**. The idea is to use manipulated T cells not only to attack the tumor, but also to help carry the therapeutic agent across the blood-brain barrier and directly to glioblastoma cells.
   
  I find this particularly interesting because it tries to address two major problems in glioblastoma at the same time: **getting an effective treatment into the brain and directing the immune system specifically against the tumor.** The treatment targets EGFRvIII, a tumor-specific alteration found in a subset of glioblastomas, which theoretically provides a way to attack tumor cells while sparing normal cells.
   
  Preclinical studies reportedly showed activity against patient-derived glioma cells and encouraging results in animal models, but we have to remember that many GBM treatments that look impressive in the laboratory ultimately fail in patients. This Phase I study is primarily designed to determine **safety and the appropriate dose**, not to prove that the treatment extends survival. It plans to enroll up to 15 adults with EGFRvIII-positive malignant glioma.
   
  Still, this is exactly the type of trial I like to see: a scientifically interesting idea has moved beyond the laboratory and is finally being tested in patients. **Now we get to find out whether the concept actually works in the human brain.**
   
  
  
• Battleship of Experiments: The Fight Against Brain Cancer        

   This is an interesting example of how advances against glioblastoma may come from **combining treatments rather than continually searching for a single “magic bullet.”** Researchers are studying whether extracellular vesicles – tiny particles that can cross the blood-brain barrier – can make glioblastoma cells more vulnerable to CAR T-cell therapy. They are using mathematical modeling and sophisticated image analysis to understand exactly how the two interact.

   
  I particularly like the multidisciplinary nature of this project. Biology, immunology, physics, mathematics and computer programming are all being brought together to attack the same problem. The researchers are even developing software to analyze hundreds of microscope images and quantify how extracellular vesicles are being absorbed by tumor cells and how that affects CAR T-cell killing.
   
  Of course, this is still early laboratory research and is a long way from proving that the combination will help patients. But glioblastoma has defeated many promising single treatments. Finding ways to intelligently combine therapies – and using computational tools to determine which combinations actually work synergistically – may be one of our best paths toward meaningful progress.
   
  
  
• Screening newborns for cancer risk        
  This is a fascinating idea, particularly for brain tumors. Researchers looked at newborn blood samples from 1,948 children who later developed a solid tumor or brain tumor by age 8 and found that about 7% carried a detectable mutation in one of 11 cancer-predisposition genes. For some brain tumors the numbers were much higher: mutations were found in about 30% of children who developed choroid plexus carcinoma, 17% with pineoblastoma and 11% with medulloblastoma.
   
  Knowing about these mutations at birth could allow doctors to monitor high-risk children closely and hopefully find a tumor when it is very small, potentially improving survival and allowing less-toxic treatment.
   
  But there is an important downside that needs to be considered. These cancers are extremely rare. The researchers estimate that only about 1 out of every 27,000 newborns would go on to develop a cancer by age 8 that could have been predicted by this 11-gene screening panel.
   
  That does not necessarily mean 26,999 children would undergo MRIs and other intensive screening to help one child. The initial genetic test would be performed on the blood spot already routinely collected from newborns, and only children found to carry a significant mutation would be referred for additional surveillance. Importantly, these mutations appear to be quite rare in healthy newborns.
   
  Still, for a child who tests positive, surveillance can become a significant burden. Depending on the particular gene, it can involve repeated physician visits, blood tests, ultrasounds, eye examinations and imaging such as MRI—sometimes beginning in infancy and continuing for years. There is also the possibility of anxiety for the family, overdiagnosis and procedures prompted by findings that ultimately prove harmless. The study authors themselves acknowledge these concerns.
   
  So I think the concept is promising, especially for syndromes where the risk of developing cancer is very high and we already know that early detection makes a difference. But before adding cancer genes to routine newborn screening, we need to know something this study cannot yet tell us: How many children need years of additional surveillance to prevent one cancer death or serious disability?
   
  Finding a genetic risk is only valuable if acting on that information does more good than harm.
  
  
• BioArctic and Mesenkia Partner to Develop Brain-Penetrant Antibody for Glioblastoma        

   This is an interesting new approach, but it is important to understand that it is still at the **preclinical research stage**—there is not yet a drug being tested in glioblastoma patients.

   
  BioArctic and Mesenkia are combining two technologies. Mesenkia has developed an antibody that targets **HVEM**, a protein found on some glioblastoma cells, including tumor stem cells that may play an important role in treatment resistance and recurrence. BioArctic is adding its **BrainTransporter** technology, which is designed to carry antibodies across the blood-brain barrier.
   
  That second part may be the most interesting. One of the major reasons many promising drugs fail in brain tumors is simply that not enough drug reaches tumor cells scattered throughout the brain. In preclinical studies, BioArctic reported that its BrainTransporter increased antibody exposure in the brain by as much as **70-fold**.
   
  If this technology really can safely deliver large antibody drugs throughout the brain, its importance could eventually extend well beyond this particular antibody. It might provide a way to revisit other promising treatments that previously could not reach adequate concentrations in the brain.
   
  However, we are a long way from knowing whether this will help patients. The companies still have to create the combined drug candidate and test it preclinically before deciding whether to move into human trials.
   
  I am encouraged by the concept, particularly because it attacks **two problems at once—finding an important target on resistant glioblastoma cells and figuring out how to get the treatment to those cells.** Now we have to see if it works.