Evaluation of next-gen CAR-T cells targeting EGFRvIII and EGFR for GBM

Brain Cancer
Marcela Maus, MD, PhD
Massachusetts General Hospital Cancer Center


Glioblastoma (GBM) is a deadly brain cancer with limited treatment options. Standard of care treatment is surgery followed by radiation and treatment with temozolomide, a chemotherapy. Standard of care has not changed in 15 years and despite treatment, most patients relapse in eight to nine months. These patients desperately need effective therapies that will prolong their lives. EGFRvIII has been found to be mutated in approximately 30% of GBM patients. This group of researchers developed CAR T-cells targeting EGFRvIII. CAR T-cell therapy is when a patient’s own T-cells (white blood cells that kill cancer cells) are collected via blood draw, then engineered to target specific cancer cells, multiplied, and infused back into the patient. However, in a phase I trial of the CAR T-cell EGFRvIII, tumor cells without the EGFR mutation remained and suppressed T-cell function. EGFR is another target that is highly abundant in about 80% of GBM patients. To overcome this, a new CAR T-cell therapy, CARv3-TEAM-E, has been developed. CARv3-Team-E targets EGFRvIII, releases a T-cell engaging molecule (TEAM) that attacks cancer cells with the unmutated EGFR, and activates more T-cells by binding to CD3. This phase I study will assess the safety of the CARv3-TEAM-E T-cells in patients with recurrent GBM with the EGFRvIII mutation, newly diagnosed GBM with the EGFRvIII mutation, and recurrent GBM without the EGFRvIII mutation.

Trial Registration: ClinicalTrials.gov Identifier: NCT05660369