Milatuzumab - a promising new immunotherapeutic agent.

Milatuzumab is a new immunotherapeutic agent targeting CD74, a membrane protein preferentially expressed in hematopoietic cancers and some solid tumors. Broad expression and fast internalization makes CD74 an ideal target for cancer therapy. We reviewed published articles about CD74 and milatuzumab. We present a comprehensive review of CD74 functions and provide explanation of milatuzumab antitumor effects. This review describes CD74 protein biology with the emphasis on the role of CD74 in tumor survival and its new role in regulation of the Fas death receptor. The development of CD74 targeting therapies to induce tumor regression and cancer cell apoptosis is described and results of clinical trials are discussed. Milatuzumab shows selective binding and rapid internalization into CD74-positive cancer cells. Milatuzumab with and without conjugated toxins synergizes with other chemotherapeutic agents and elicits significant antitumor effects in mice. In a Phase I trial, milatuzumab showed no severe adverse effects in patients with relapsed/refractory multiple myeloma and it stabilized the disease in some patients for up to 12 weeks. Ongoing trials testing different treatment schedules of milatuzumab in chronic lymphocytic leukemia, non-Hodgkin's lymphoma and multiple myeloma indicate that milatuzumab shows no severe adverse effects in humans.