Monoclonal antibody therapy of haematological malignancies

Over the past decade the potential for delivering targeted therapy against malignant disease by the use of monoclonal antibodies (MAbs) has begun to be realised. Haematological malignancies, because of the relative accessibility of the malignant cell in blood and bone marrow and the understanding of haemopoietic lineage-specific antigens, have provided a successful testing ground for this therapy. There have been many technical developments which have allowed the safe delivery of more potent antibody constructs. The development of human or chimeric antibodies has largely overcome the problems associated with host immune responses to rodent-derived MAbs. Protein engineering to combine MAbs with other biologically active molecules such as radioisotopes, toxins, chemotherapy and cytokines, has made available a new range of agents with clinical activity. The purpose of this review is not to give a catalogue of all therapeutic antibodies but rather to outline the principles of this approach, the current state of knowledge, and possible directions for future development. First, the general requirements and strategies for use of both unmodified and conjugated MAbs are discussed, followed by a summary of the trial data in specific lymphoid and myeloid haemopoietic malignancies. The focus is on MAbs that now have an accepted use in clinical practice, with some discussion of newer MAbs under development. Vaccination strategies and the role of MAbs in bone marrow transplantation are not discussed in detail. The trials of the next decade will address issues such as: whether clinical activity translates into improved survival; the optimal strategies and timing for clinical use; whether increasing potency of MAbs (as in radio- and immunoconjugates) will increase toxicity and, finally, what other potential molecules, such as those influencing cell growth and death, may be targeted.