Miguel Bronchud, Veteran Cancer Clinician, Researcher, Co-Founder and ex Advisory Board at Regenerative Medicine Solutions, shared a post on LinkedIn:
New promising and exciting results of cellular immunity therapy in incurable brain cancer of children?
In children, the most fatal cancers occur inside the brain. When a tumor grows in an area like the brainstem, like a diffuse intrinsic pontine glioma (DIPG), surgical removal risks damaging sensitive tissue that regulate essential functions like breathing.
Even without surgery, treatment can still be highly invasive. Getting drugs across the blood-brain barrier often requires injections into the brain or cerebrospinal fluid, and chemotherapy is notoriously difficult for children to tolerate. Thus, patients are often stuck without good treatment options.
A new Phase 1 trial led by researchers at Children’s National Hospital showed that a new autologous multi-antigen T cell therapy can be delivered intravenously and reach the brain through the bloodstream to fight off brain tumors in children.
With results, published in Nature Medicine:
The tumor-associated antigens (TAAs) WT1, PRAME and surviving are widely expressed by these tumors, and a manufacturing technique has been developed to target these intracellular TAAs using autologous, nongenetically engineered T cells.
- “ReMIND, an open-label, phase 1 adaptive dose-finding study to determine the safety/feasibility of autologous, systemically administered trivalent T cells targeting WT1, PRAME and survivin in children with CNS tumors.”
- Eligible patients had newly diagnosed diffuse intrinsic pontine glioma without lymphodepletion (arm A, n = 16 enrolled, n = 11 infused) and relapsed/recurrent nonbrainstem CNS malignancies without (arm B, n = 28 enrolled, n = 18 infused) or with (arm C, n = 7 enrolled, n = 4 infused) lymphodepletion.
- Primary end points were safety, feasibility and maximum tolerated dose determination; secondary end points included preliminary efficacy and immunobiological correlates, including in vivo TAA-T persistence and systemic immune activation.
- Dose level 3 (8 × 107 cells per m2 per dose) was determined as the maximum tolerated dose.
- Treatment was well tolerated with fatigue and headache being the most common adverse events, although two possibly related serious adverse events of tumor swelling occurred.
- One grade 5 event in a patient with diffuse intrinsic pontine glioma with hydrocephalus, tumor edema and respiratory failure was categorized as a dose-limiting toxicity.
- Median overall survival for arm A was 13.7 months from diagnosis (range, 6.2–32.0) and median progression-free survival for arms B/C was 5.0 months from infusion (range, 0.5–51.6).
- Three patients in arms B/C are alive without disease at 31.8, 41.2 and 51.6 months without further treatment, including one complete response. This trial met safety/feasibility primary end points with some preliminary signals of efficacy.
Read more articles about DIPG on OncoDaily.