Sep 6, 2018

Immunotherapy shows early promise against brain cancers

MRI of a patient with a glioblastoma tumor. Photo: BSIP/UIG via Getty Images

An international team of scientists say they've developed a molecule that can target the two most common brain cancers, successfully slowing down tumor growth in a pre-clinical study on animals published in Nature Wednesday.

Why it matters: The targeted brain cancers — adults' glioblastoma and children's medulloblastoma — are aggressive cancers often fatal within 2 years (as seen when glioblastoma claimed the life of Sen. John McCain). This team hopes this new method, which successfully breaches the blood-brain barrier, may be an important step forward in finding an effective treatment.

Background: Glioblastoma and medulloblastoma tumors are often deep in the brain where it's difficult to surgically remove them. Immunotherapies are thought by many to offer great promise in treating the tumors, but they face many challenges, including safely breaching the blood-brain barrier.

The barrier offers important protection for the brain, but can keep out drugs that doctors want to send to the brain to trigger the body's own immune system to fight the cancer.

What they did: The team first determined the best way to breach the brain barrier by studying the mechanism used by another disease, multiple sclerosis, to get around the barrier.

  • Then, "using lessons learned from MS," they developed a molecule that can get around the barrier by attaching to certain cells of the barrier (known as ALCAM), study co-author Nabil Ahmed tells Axios.
  • The T-cells are engineered to bind to an antigen produced by the cancer (called HER2), allowing it to locate and attack the tumors.

What they found: In testing in mice, the molecule, known as HS-CD6, "robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumor activity," the study states.

  • The therapy did not appear to be toxic, which is a common failing of immunotherapies, as the mice lived longer. In addition, the therapy appeared to only attack the tumor sites, the authors said.
"The HS molecule that can overcome this [blood-brain] obstacle is a first-in-class; no similar molecules have been previously described. ... I am quite excited about the possible advantage of this to patients with incurable brain cancers that could hopefully benefit from using this in the clinic."
— Nabil Ahmed, Baylor College of Medicine

Outside comment: Two experts not involved with the study say these results show promise, but are a first step towards a bigger goal.

"This study represents a major leap forward in our understanding of [trafficking T cells] to brain tumors... Engineering T cells to overcome mechanistic barriers to tumor infiltration, the authors demonstrate a marked increase in tumor-infiltrating lymphocytes and increased efficacy of a [CAR-T] cell therapy. This is an elegant study with exciting implications for therapy of these lethal cancers." 
— Michelle Monje-Deisseroth, associate professor of neurology, Stanford University
"This study lays out a viable strategy for immunotherapy in glioblastoma. But key challenges must be overcome before we can translate the discovery from mice to patients. For instance, ALCAM is expressed by a variety of cell types, including bone-marrow cells. More studies will be required."
— Michael Platten, of Heidelberg University, in a News and Views piece in Nature

What's next: Ahmed tells Axios they are currently working on securing approvals from regulatory bodies to test this on humans with hard-to-treat or incurable brain cancers.

Go deeper: Read the National Cancer Institute's in-depth look at challenges facing glioblastoma and immunotherapy.

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