Monoclonal antibody therapies in leukemias

Abstract

Significant advances in the development of monoclonal antibodies (unconjugated) and monoclonal antibodies conjugated to potent toxins or cytotoxic agents (immunoconjugates) have enabled improved targeting of leukemic cells with acceptable toxicities. Gemtuzumab ozogamicin, a calicheamicin-conjugated anti-CD33 monoclonal antibody, has demonstrated substantial efficacy in patients with acute myeloid leukemia (AML) and has induced remissions in patients with favorable-, intermediate-, and poor-risk cytogenetics. The immunoconjugate BL-22, comprised of an anti-CD22 monoclonal antibody fused to a fragment of pseudomonas exotoxin PE38, has produced high response rates in patients with purine analog-resistant hairy cell leukemia. Campath-1H (Wellcome, Beckenham, UK, and Ilex Oncology, San Antonio, TX), an anti-CD52 monoclonal antibody, has demonstrated significant activity in patients with previously untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL), as well as in patients with T-cell prolymphocytic leukemia. The anti-CD20 monoclonal antibody rituximab also is effective in treating CLL and is being evaluated in combination with chemotherapeutic agents (cyclophosphamide) and fludarabine. Monoclonal antibodies may sensitize cells to chemotherapy. The optimal role of targeted therapy with monoclonal antibodies and immunoconjugates in acute and chronic leukemias has not yet been determined, but these novel therapies are beginning to fulfill their promise.