Zanolimumab (Humax-CD4), a fully human monoclonal antibody with significant clinical responses in cutaneous T-cell lymphoma

Abstract

Zanolimumab (HuMax-CD4, Genmab, Copenhagen, Denmark) is a fully human monoclonal anti- CD4 antibody that targets the CD4 molecule on malignant Tcells in cutaneous T-cell lymphoma. Zanolimumab inhibits CD4+ T cells by combining signaling inhibition with antibody dependent cellular cytotoxicity (ADCC). T cell activation is inhibited by a fast dual mechanism in which the antibody abrogates signaling via the T cell receptor and, in addition, down regulates T cell activation by transmission of direct inhibitory signals. Zanolimumab induces killing of CD4+ T cells via ADCC by NK cells to which memory type (CD45RO+ CD4+) T cells are more sensitive than naive (CD45RA CD4+) cells [Rider et al. Cancer Res 2007;67:9945-53] This latter observation may be of particular relevance for the treatment of cutaneous t-cell lymphoma (CTCL) which typically comprise CD45RO memory-type cells.