Hope for Glioblastoma Patients

It’s wonderful to learn that there is hope for Glioblastoma patients.  The study below shows good response to treatment in mouse models, with long term benefits.

First, let’s define a term used in the Abstract, NKG2D:

NKG2D is one of the most intensively studied immune receptors of the past decade. Its unique binding and signaling properties, expression pattern, and functions have been attracting much interest within the field due to its potent antiviral and anti-tumor properties. As an activating receptor, NKG2D is expressed on cells of the innate and adaptive immune system.
— https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192283/

In a 2007 study showed that this is a viable therapy for Ovarian Cancer as well.  https://www.ncbi.nlm.nih.gov/pubmed/17510432

NKG2D-based CAR-T cells and radiotherapy exert synergistic efficacy in glioblastoma

Abstract - 2017 Dec 8

Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models.

ChNKG2D T cells demonstrated high IFN-γ production and cytolytic activity in vitro. Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor re-challenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T cell treatment resulted in synergistic activity in 2 independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions.

We thus provide preclinical proof-of-concept of NKG2D CAR T cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.

Author information - WeissWellerGuckenbergerSentman Roth

  1. Department of Neurology, University Hospital Zurich tobias.weiss@usz.ch.
  2. Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich.
  3. Radiation Oncology, University Hospital Zurich.
  4. Department of Microbiology & Immunology, The Geisel School of Medicine at Dartmouth.