Genmab drug more effective than rituximab

HuMax-CD20 is capable of attacking more targets expressing low levels of CD20, a molecule implicated in lymphoid tumors, than rituximab. When low levels of CD20 are present on tumor targets, rituximab does not appear effective in killing the tumor cells. HuMax-CD20, however, is effective when CD20 is expressed at both high and very low levels.

HuMax-CD20 is a fully human, high-affinity antibody that targets the CD20 molecule in the cell membrane of B-cells. In certain types of cancer, these cells can proliferate causing the need for treatment to reduce the number of B-cells.

The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin.

A panel of cell lines expressing varying amounts of CD20 molecules per cell was generated by retroviral transduction of CEM tumor cells. HuMax-CD20 appeared to be highly superior in the induction of complement-mediated lysis of cells for all CD20 expression levels as compared to rituximab. HuMax-CD20 appeared to induce significant lysis of cells at the lowest CD20 expression level tested, whereas such cells seemed resistant to rituximab. Complete lysis was achieved by HuMax-CD20 at intermediate expression levels of CD20, whereas complete lysis with rituximab was not achieved.

Genmab is currently conducting phase II and III clinical trials of the drug. Two studies and examining the treatment cancer involving B-cells (non-Hodgkin’s lymphoma and chronic lymphocytic leukemia) and is being conducted in patients with active rheumatoid arthritis. The company has already received encouraging results from a clinical trial in patients with relapsed or refractory follicular lymphoma.