Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy

• DOI: 10.1172/jci.insight.134612
• Publication Date: 2020-06-02T18:19:57Z
• Authors: Pei-Hsuan Chen; Mikel Lipschitz; Jason L. Weirather; Caron Jacobson; Philippe Armand; Kyle Wright; F. Stephen Hodi; Zachary J. Roberts; Stuart A. Sievers; John Rossi; Adrian Bot; William Go; Scott J. Rodig
• Keywords: Cell therapy; Cytokine Release Syndrome

Mechanisms of chimeric antigen receptor (CAR) T cell-mediated antitumor immunity and toxicity remain poorly characterized because few studies examine the intact tumor microenvironment (TME) following CAR cell infusion. Axicabtagene ciloleucel is an autologous anti-CD19 therapy approved for patients with large B lymphoma. We devised multiplex immunostaining ISH assays to interrogate cells other immune infiltrates in biopsies diffuse lymphoma axicabtagene found that a majority intratumoral expressed markers activation but, unexpectedly, constituted ≤5% all within TME 5 days or more after therapy. Large numbers without were also activated infusion; these positive Ki-67, IFN-γ, granzyme (GzmB), and/or PD-1 at highest levels cells. Additionally, non-CAR exclusive source IL-6, cytokine associated release syndrome, their These data suggest are both beneficial pathological effects.