Lenzilumab Overview

Introduction of Lenzilumab

Lenzilumab (alternative identifier KB003) is a humanized monoclonal antibody (class IgG1 kappa) developed by Humanigen, Inc. (formerly known as KaloBios Pharmaceuticals Inc.). It was designed to target and neutralize circulating granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), the myeloid inflammation factor involved in the recruitment of myeloid cells to a tumor and a central actor in leukocyte differentiation, autoimmunity and inflammation. There is also extensive evidence linking GM-CSF expression to serious and potentially life-threatening side effects in chimeric antigen receptor T-cell (CAR-T) therapy, such as neurotoxicity and Cytokine Release Syndrome (CRS). Humanigen is working with leading CAR-T experts to develop lenzilumab as a potential prophylactic therapy to optimize treatment and minimize or prevent neurotoxicity associated with CAR-T cancer therapy. In addition, lenzilumab is currently being evaluated as a potential treatment for rare leukemias in a phase I trial (NCT02546284) in patients with chronic myelomonocytic leukemia (CMML), with additional potential in juvenile myelomonocytic leukemia (JMML), a rare pediatric cancer. In previous clinical trials, lenzilumab has shown to be safe and well tolerated in more than 100 patients, including those with rheumatoid arthritis, asthma and healthy volunteers. It is a potent inhibitor of GM-CSF in vivo.

Mechanism of Action of Lenzilumab

GM-CSF is a monomeric glycoprotein that functions as a cytokine — it is a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection. GM-CSF also has some effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface. GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity. Thus, GM-CSF facilitates development of the immune system and promotes defense against infections. GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract. Lenzilumab targets and neutralizes circulating GM-CSF, inhibiting GM-CSF-involved immune response, including the recruitment of myeloid cells to a tumor, leukocyte differentiation, autoimmunity and inflammation.

Fig 1. Mechanism of Action of Lenzilumab

Table 1. Clinical Projects of Lenzilumab *

What We Provide

Therapeutic Antibody

Lenzilumab

We provide high-quality Lenzilumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Lenzilumab

For research use only. Not intended for any clinical use.