Immunotherapy in adult acute lymphoblastic leukemia: the role of monoclonal antibodies

Abstract

The past decade has witnessed major advances in the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Monoclonal antibodies (MoAbs) targeting specific leukemic cell surface antigens (eg, CD20, CD22, and CD19) represent a significant breakthrough in the ALL therapeutic armamentarium (Table 1). MoAbs bind to a specific target on leukemic cells that has relatively lower expression on normal cells. They work through a number of mechanisms, including antibody-dependent and complement-dependent cytotoxicity and direct induction of apoptosis. If a target is known to internalize upon binding, potent drugs or toxins can be conjugated to the antibody portion, producing an additional mechanism for leukemic cell–targeted elimination. The anti-CD20 antibody rituximab has produced encouraging results as a component of the initial B-cell ALL (B-ALL) therapy. Other MoAbs targeting CD19 and CD22 have been evaluated in clinical trials of refractory/relapsed ALL (Table 2). The promising results have led to combining these MoAbs with standard chemotherapy in ALL salvage and first-line regimens. With the recent development of CD19-direct chimeric antigen receptor (CAR) T cells that are capable of producing deep and lasting remissions in patients with multiply refractory ALL, the question arises: How should we best prioritize the use of these various tools against ALL to maximize efficacy? Herein, we review the clinical activity of MoAbs in adult ALL and discuss the relative roles of MoAbs and CAR T cells in modern ALL therapy. Anti-CD20