CD123-CAR T cell therapy

P1, N=32, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting

P1, N=32, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2025 --> May 2026 | Trial primary completion date: Jul 2024 --> May 2025

P1, N=32, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

Our findings reveal that the TME of our immune competent leukemia CAR T cell therapy models recapitulate human disease, showing an increase in dying tumor cells within the bone marrow of mice in the treated group, with a number of other populations (e.g. dendritic cells, regulatory T cells) approximating the tumor-only microenvironment profile.We have developed the first functional mCD123-CAR T cells targeting mouse AML and ALL and have shown their activity in immunocompetent models, with potent anti-leukemic activity in vitro and in vivo with minimal toxicity. Our model will provide insight into the impact of the AML TME on CAR T cell functionality and inform future strategies to improve CAR T cells in the immunosuppressive TME.

Patients received Fludarabine/Cyclophosphamide prior to a single CAR T cell infusion. Conclusions Our initial clinical experience with CD123-CAR T cells demonstrates feasibility, safety, and evidence of anti-leukemic activity. Upcoming CD123-CAR T cell products will be manufactured with dasatinib to limit T cell differentiation and exhaustion thereby enhancing our CD123-CAR T cell therapy approach.

To date, preclinical evaluation of CD123-CAR T cells have used human xenograft models, which lack a functional immune system...To determine in vivo toxicity of mCD123-CAR T cells, non-tumor bearing C57BL/6 mice were given 200 mg/kg cyclophosphamide (Cy) and one effector T cell infusion generated from transgenic luciferase mice (N=5) and monitored by bioluminescence imaging for 10 days...mCD123-CAR T cells demonstrated potent anti-leukemic activity in vitro and have anti-leukemia activity with minimal to no toxicity in vivo. These findings will provide insight into the impact of the AML TME on CAR T cell functionality, and inform future strategies to improve CAR T cells in the immunosuppressive TME.

We evaluated the LigandCD70.CAR in combination with a CLL-1.CAR and a CD123.CAR, as both have shown preclinical efficacy and are currently being tested in clinical trials...The simultaneous targeting of two AML antigens may thus mitigate the risk of antigen-negative relapse. These data indicate that the Ligand70.CAR combined with other AML targeting CARs could be an effective therapeutic option for AML.

Patients received lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide followed by a single CAR T cell infusion. Conclusions Our initial clinical experience with CD123-CAR T cells for pediatric patients with r/r AML demonstrates feasibility, safety, and evidence of anti-leukemic activity. Upcoming CD123-CAR T cell products will be manufactured in the presence of dasatinib to limit T-cell differentiation and exhaustion as we continue to explore our CD123-CAR T cell therapy approach for pediatric r/r AML.

P1, N=32, Not yet recruiting, St. Jude Children's Research Hospital