UCLA studies link T-cell activity to longer survival in recurrent glioblastoma
A UCLA-led phase 2 trial of 63 people with recurrent glioblastoma found that nivolumab plus ipilimumab before surgery produced greater immune activity in tumours than nivolumab alone. Medical Xpress reports median survival of about 13.5 months with the combination, versus roughly nine months with nivolumab alone; LA Wire cautions that survival was a secondary outcome and the trial did not establish a definitive benefit. A separate study developed a mouse model that reproduced key features of glioblastoma’s resistance to immunotherapy.
Bottom line — Five patients in the combination-treatment groups became long-term survivors, but UCLA’s trial does not establish that the regimen improves survival.
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Medical Xpress reports that tumours with the highest T-cell density were associated with longer survival, and that the combination increased T-cell infiltration and interferon-related immune activity.
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LA Wire says 58 of the 63 randomised participants received trial medication; survival analysis combined groups with different treatment schedules.
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The studies were published in Nature Communications and Cancer Research, according to Medical Xpress.
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The new mouse model used MADR technology and included EGFRvIII alongside loss of the tumour-suppressor genes PTEN and CDKN2A, Medical Xpress reports.
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In the model, tumours had few T cells and resisted checkpoint blockade; researchers also found tumour cells resisted T-cell killing and promoted T-cell exhaustion, according to Medical Xpress.
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UCLA researchers are investigating brain-penetrant EGFR inhibitors and developing mRNA vaccines intended to increase T-cell infiltration, Medical Xpress reports.