Dacetuzumab Overview

Introduction of Dacetuzumab

Dacetuzumab (also known as SGN-40 or huS2C6), derived from the murine antibody - S2C6, is an immunoglobulin G1 humanized monoclonal antibody (mAb), which could target the CD40 antigen. It is in development by Seattle Genetics Inc and licensee Genentech Inc for the potential treatment of hematological malignancies. Dacetuzumab has been used in trials studying the treatment of Multiple Myeloma, Non-Hodgkin Lymphoma, Leukemia, Lymphocytic, Chronic, and Lymphoma, Large B-Cell, Diffuse. In vitro, dacetuzumab exhibited antitumor activity against several B-cell lymphoma and multiple myeloma (MM) cell lines, and induced direct apoptosis as well as the engagement of effective antibody-dependent cell-mediated cytotoxicity. In vivo, dacetuzumab demonstrated enhanced antitumor efficacy in combination with other mAbs and chemotherapeutic agents; many of these combinations are now being tested clinically. Early clinical trials have evaluated the pharmacokinetics, safety and efficacy of dacetuzumab monotherapy in patients with relapsed/refractory B-cell lymphomas or MM. Targeting CD40 with dacetuzumab resulted in modest antitumor activity in B-cell lymphomas and, to a lesser extent, in MM. In particular, patients with diffuse large B-cell lymphoma responded well to dacetuzumab; the drug is being pursued for this indication in phase II trials.

Mechanism of Action of Dacetuzumab

CD40 is a type-1 transmembrane protein of the tumor necrosis factor receptor superfamily that functions as a co-stimulatory molecule upon interaction with its ligand CD154 (CD40L). CD40 is expressed on B cells and their progenitors, epithelial and endothelial cells, and many antigen-presenting cells (dendritic cells, activated B lymphocytes, and activated monocytes). In addition, CD40 is expressed on most malignancies of B-cell origin, including NHL, multiple myeloma, and chronic lymphocytic leukemia. The high prevalence of CD40 expression on B-cell malignancies makes it an attractive potential tumor target for antibody-based cancer therapy. Dacetuzumab is a humanized IgG1 form of S2C6, a murine anti-human CD40 monoclonal antibody (mAb). In contrast to blocking anti-CD40 mAbs, dacetuzumab does not prevent CD40/CD40L interactions, and the antibody behaves as a partial agonist in vitro. Dacetuzumab has little effect on normal cells in vitro, but in the presence of cross-linking reagents and certain cytokines or growth factors (e.g., interleukin-4 [IL-4]), it enhances the proliferation of responsive cells, such as normal B-cells. In vitro and in vivo studies with the CD40-positive lymphoma lines Ramos and IM-9 demonstrated that dacetuzumab induces apoptosis and inhibits growth of CD40-positive lymphoma lines through direct signal transduction and kills tumor cells through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). The relevance of both direct and cell-mediated mechanisms was apparent in in vivo models. It has been demonstrated that agonistic CD40 antibodies may mediate antitumor activity through activation of CD40-positive antigen presenting cells, including dendritic cells.

Fig 1. Mechanism of Action of Dacetuzumab

Table 1. Clinical Projects of Dacetuzumab*

What We Provide

Therapeutic Antibody

Dacetuzumab

We provide high-quality Dacetuzumab 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?term=Dacetuzumab

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