Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia

Role of CD154 in cancer pathogenesis and immunotherapy

“…The Ab was shown to induce ADCC of myeloma cells in vitro, as well as to diminish some CD154-mediated events such as activation of survival signals including Akt, NF-jB, and ERK, adhesion to fibronectin and bone marrow stromal cells, and secretion of IL-6 and VEGF, factors directly related to angiogenesis [117]. Locatumumab was also assessed in another phase I study, where treating 26 CLL patients with this antagonistic anti-CD40 Ab yielded partial response in only one patient however was capable of inducing stable disease in more than half of the participating patients [118]. These data are promising but suggest that subsequent clinical trials should rather evaluate the therapeutic efficiency of Locatumumab in combination with other anti-tumorigenic agents.…”

Biological Therapy of Cancer

“…Lucatumumab (HCD122), a fully humanized antibody against the antigen CD40, entered a phase I clinical trial for CLL. 5 Alemtuzumab (Campath ® ) is a humanized monoclonal antibody that binds to CD52 (an antigen expressed on B and T lymphocytes) that was approved in ), which is expressed in epithelial tissues, human blood dendritic cells (DCs), and T cells. MUC1 is a heavily O-glycosylated transmembrane protein that is overexpressed in 90% of breast cancers and also in prostate cancer.…”

Obinutuzumab For The Treatment Of Indolent Lymphoma

“…Anti-CD19 monoclonal antibodies show efficacy when they are conjugated to either a cytotoxic agent, such as in SAR3419 [38,39], or another antibody fragment, such as in the bispecific T-cell-engaging antibody blinatumomab [40]. Otlertuzumab as anti-CD37 monoclonal antibody [41,42] and lucatumumab as anti-CD40 monoclonal antibody showed modest clinical activity [43,44]. These antibodies remain investigational and CD20 antigen still remains by far the most successful target up to now.…”