Generation and administration of autologous T cells transduced with a 3rd generation GD2 chimeric antigen receptor for patients with relapsed or refractory neuroblastoma

      Administration of T cells modified with a 1st generation chimeric antigen receptor (CAR) targeting GD2 has been safe and can produce clinical responses, including prolonged complete remissions. Although responses were more frequent, and progression free survival was longer in patients in whom CAR-T cells could be detected for ≥ 6 weeks after infusion, these cells were only present at very low frequency in peripheral blood. Increasing the in vivo proliferation of GD2 T cells after adoptive transfer may lead to improved T cell to tumor cell ratios, increasing anti-tumor activity and improving patient survival. We therefore incorporated the OX40 and CD28 co-stimulatory endodomains into our GD2-CAR construct in the hope they would enhance in vivo expansion and persistence of CAR T-cells in patients with relapsed/refractory neuroblastoma.
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