2:54 PM
Apr 16, 2018
 |  BC Extra  |  Preclinical News

Anti-GD2 CAR T could treat midline gliomas

A study published in Nature Medicine suggests that CAR T cells targeting ganglioside GD2 could help treat diffuse midline gliomas with mutated histone H3 K27M.

GD2 has been identified as a target to treat cancers such as neuroblastoma. However, treatment options are limited for diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas with the H3 K27M mutation -- aggressive and fatal pediatric brain cancers.

Scientists from Stanford University School of Medicine identified high GD2 expression in cell cultures from patients with H3 K27M mutant DIPG compared with wild-type H3 gliomas.

In vitro, anti-GD2 CAR T cells increased cytokine production and reduced DIPG cell growth compared with anti-CD19 CAR T cells as control.

In five patient-derived xenograft mouse models of H3 K27M mutant diffuse midline gliomas, intravenous anti-GD2 CAR T cell therapy decreased tumor growth compared with control anti-CD19 CAR T cells. In one model, anti-GD2 CAR T cell therapy increased survival compared with control. However, the anti-GD2 CAR T led to peritumoral neuroinflammation and hydrocephalus in some mice, resulting in death.

Lead author Crystal Mackall told BioCentury that clinical testing of the anti-GD2 CAR T cell therapy to treat DIPG is expected to begin by year end or in 1Q19 at Stanford. Mackall is professor of pediatrics and medicine at Stanford and director of the Stanford Center for Cancer Cell Therapy and the Parker Institute for Cancer Immunotherapy.

The authors noted that successful clinical translation will require careful patient monitoring and potential interventions to manage neuroinflammation. Mackall told BioCentury that the trial will include "intensive monitoring with therapeutic intervention for increased intracranial pressure." Additionally, the CAR T therapy incorporates a "suicide domain" that can be activated with a small molecule in the event of life-threatening toxicity.

At least two companies are developing anti-GD2 CAR T cell therapies.

Autolus Ltd. (London, U.K.) said in March that preliminary data from its anti-GD2 CAR T cell therapy showed "early signs of clinical activity" in a Phase I trial to treat pediatric patients with neuroblastoma. The company will present the data at the American Association for Cancer Research meeting in Chicago on Tuesday. Autolus has worldwide, commercialization rights to the therapy from University College London.

Beijing Sinobioway Group Co. Ltd. (Beijing, China) has GD2-targeted CAR T cells in Phase I/II testing to treat refractory or relapsed neuroblastoma.

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