Last update 01 Nov 2024

CD33 x CLL-1 x CD19

Last update 01 Nov 2024

Basic Info

Related Targets

CD33CLL-1CD19

Drugs associated with CD33 x CLL-1 x CD19

ALETA-004

Target

CD19 x CD33 x CLL-1

Mechanism

CD19 inhibitors [+4]

Active Org.

Aleta Biotherapeutics, Inc.Startup

Originator Org.

Aleta Biotherapeutics, Inc.Startup

Active Indication

Acute Myeloid Leukemia [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD33 x CLL-1 x CD19

100 Translational Medicine associated with CD33 x CLL-1 x CD19

0 Patents (Medical) associated with CD33 x CLL-1 x CD19

Literatures (Medical) associated with CD33 x CLL-1 x CD19

01 Jan 2023·Open medicine (Warsaw, Poland)

Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia.

Article

Author: Gao, Yajing ; Wang, Hui ; Zhao, Wei ; Wu, Xueying ; Gong, Meiwei ; Fu, Minjing ; Chen, Man ; Wang, Aixian

Full spectrum flow cytometry brings a breakthrough for minimal residual disease (MRD) detection in acute myeloid leukemia (AML). We aimed to explore the role of a new panel in MRD detection. We established a 24-color full-spectrum flow cytometry panel. A tube of 24-color antibodies included CD45, CD117, CD34, HLA-DR, CD15, CD64, CD14, CD11c, CD11b, CD13, CD33, CD371, CD7, CD56, CD19, CD4, CD2, CD123, CD200, CD38, CD96, CD71, CD36, and CD9. We discovered that when a tube meets 26 parameters (24 colors), these markers were not only limited to the observation of MRD in AML, but also could be used for fine clustering of bone marrow cells. Mast cells, basophils, myeloid dendritic cells, and plasmacoid dendritic cells were more clearly observed. In addition, immune checkpoint CD96 had the higher expression in CD117+ myeloid naive cells and CD56dimNK cells, while had the lower expression in CD56briNK cells in AML-MRD samples than in normal bone marrow samples. CD200 expression was remarkably enhanced in CD117+ myeloid naive cells, CD4+ T cells, T cells, activated T cells, CD56dimNK cells, and CD56briNK cells in AML-MRD samples. Our results can be used as important basis for auxiliary diagnosis, prognosis judgment, treatment guidance, and immune regulation in AML.

01 Mar 2022·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL

Q2 · MEDICINE

ArticleOA

Author: Osburg, Lukas ; Mueller, Stefanie ; Li, Bochong ; Salih, Helmut R ; Michaelson, Jennifer S ; Mehta, Naveen K ; Sindel, Isabelle ; Heitmann, Jonas S ; Pfluegler, Martin ; Marklin, Melanie ; Baeuerle, Patrick A ; Bühring, Hans-Jörg ; Jung, Gundram ; Meetze, Kristan ; Zekri, Latifa ; Kauer, Joseph ; Hörner, Sebastian ; Vogt, Fabian

BackgroundIn lymphoid malignancies, the introduction of chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) has achieved remarkable clinical success. However, such immunotherapeutic strategies are not yet established for acute myeloid leukemia (AML), the most common form of acute leukemia in adults. Common targets in AML such as CD33, CD123, and CLEC12A are highly expressed on both AML blasts and on normal myeloid cells and hematopoietic stem cells (HSCs), thereby raising toxicity concerns. In B-cell acute lymphoblastic leukemia (B-ALL), bsAbs and CAR-T therapy targeting CD19 and CD22 have demonstrated clinical success, but resistance via antigen loss is common, motivating the development of agents focused on alternative targets. An attractive emerging target is FLT3, a proto-oncogene expressed in both AML and B-ALL, with low and limited expression on myeloid dendritic cells and HSCs.MethodsWe developed and characterized CLN-049, a T cell-activating bsAb targeting CD3 and FLT3, constructed as an IgG heavy chain/scFv fusion. CLN-049 binds the membrane proximal extracellular domain of the FLT3 protein tyrosine kinase, which facilitates the targeting of leukemic blasts regardless of FLT3 mutational status. CLN-049 was evaluated for preclinical safety and efficacy in vitro and in vivo.ResultsCLN-049 induced target-restricted activation of CD4+ and CD8+ T cells. AML cell lines expressing a broad range of surface levels of FLT3 were efficiently lysed on treatment with subnanomolar concentrations of CLN-049, whereas FLT3-expressing hematopoietic progenitor cells and dendritic cells were not sensitive to CLN-049 killing. Treatment with CLN-049 also induced lysis of AML and B-ALL patient blasts by autologous T cells at the low effector-to-target ratios typically observed in patients with overt disease. Lysis of leukemic cells was not affected by supraphysiological levels of soluble FLT3 or FLT3 ligand. In mouse xenograft models, CLN-049 was highly active against human leukemic cell lines and patient-derived AML and B-ALL blasts.ConclusionsCLN-049 has a favorable efficacy and safety profile in preclinical models, warranting evaluation of its antileukemic activity in the clinic.

01 Oct 2021·Molecular Cancer TherapeuticsQ2 · MEDICINE

Anti-CD19 CAR T Cells That Secrete a Biparatopic Anti-CLEC12A Bridging Protein Have Potent Activity Against Highly Aggressive Acute Myeloid Leukemia In Vitro and In Vivo

Q2 · MEDICINE

Article

Author: Birt, Alyssa ; Su, Lihe ; Lobb, Roy R ; Rennert, Paul D ; Sanford, Tom ; Ambrose, Christine ; Wu, Lan ; Dufort, Fay J

AbstractRefractory acute myeloid leukemia (AML) remains an incurable malignancy despite the clinical use of novel targeted therapies, new antibody-based therapies, and cellular therapeutics. Here, we describe the preclinical development of a novel cell therapy that targets the antigen CLEC12A with a biparatopic bridging protein. Bridging proteins are designed as “CAR-T cell engagers,” with a CAR-targeted protein fused to antigen binding domains derived from antibodies. Here, we created a CD19-anti-CLEC12A bridging protein that binds to CAR19 T cells and to the antigen CLEC12A. Biparatopic targeting increases the potency of bridging protein-mediated cytotoxicity by CAR19 T cells. Using CAR19 T cells that secrete the bridging protein we demonstrate potent activity against aggressive leukemic cell lines in vivo. This CAR-engager platform is facile and modular, as illustrated by activity of a dual-antigen bridging protein targeting CLEC12A and CD33, designed to counter tumor heterogeneity and antigen escape, and created without the need for extensive CAR T-cell genetic engineering. CAR19 T cells provide an optimal cell therapy platform with well-understood inherent persistence and fitness characteristics.

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