First-in-human CLL1-CD33 compound CAR T cells

<p class="article-intro">A study presented at the EHA Annual Meeting investigates the anti-leukemic activity of the CLL1-CD33 compound CAR (cCAR) in vitro and in vivo in order to offer treatment opportunities for refractory and relapsed acute myeloid leukemia (AML) patients.</p> <hr /> <p class="article-content"><p>CAR T cell therapies for CD19⁺ lymphoid malignancies have recently shown success in clinical studies. CAR T cells for myeloid malignancies including acute myeloid leukemia are still being explored in (pre)clinical trials.</p> <p>In the presented study a compound CAR was generated that contains two independent complete units targeting CD33 for a bulky leukemia and CLL1 for leukemic stem cells. In vitro assays indicated that CLL1-CD33 cCAR had specific anti-tumor activity against cell lines engineered expressing CLL1 or CD33, as well as leukemia samples from AML patients.</p> <p>In mouse models generated by cell lines engineered expressing CLL1 or CD33 and AML cell line U937 cells, the cCAR T cells significantly reduced tumor burden and prolonged survival. CD52 specific antibody CAMPATH could be used as a safety-switch to rapidly terminate cCAR therapy in mouse models. In the first-in-human phase-I-trial, CLL1-CD33 cCAR T cell therapy was safe and well tolerated, and achieved complete response (CR).</p> <p>This preclinical study has shown that the CLL-1-CD33 cCAR possesses consistent, specific, and potent anti-tumor activity against CLL-1⁺ and/or CD33⁺ leukemia cells in vitro and in vivo. cCAR may have advantages over single-CAR therapy in terms of reduction of disease relapse by targeting LSC and bulky AML population. Phase-I-trial for CLL-1-CD33 cCAR are underway.</p> <p><strong>Reference:</strong> <br /> <em>Liu F: First in human CLL1-CD33 compound CAR T cells as a two-pronged approach for the treatment of refractory acute myeloid leukemia. EHA Annual Congress, abstract # S149</em></p></p>