For many years,
alkylating agents and
purine nucleoside analogs (PNA) have been considered the
drug of choice for treatment of
chronic lymphocytic leukemia (CLL). More recently the introduction of
monoclonal antibodies (mAb), especially
rituximab directed against CD20 and
alemtuzumab directed against CD52, has renewed interest in CLL
therapy. Over the last few years, several new mAbs directed against lymphoid cells have been developed and investigated in preclinical studies and clinical trials. Some of them are highly active in CLL. New mAbs directed against CD20 include human mAb
ofatumumab (HuMax CD20),
IMMU-106 (
hA20) which has a >90% humanized framework and
GA-101, a novel third - generation fully humanized and optimized mAb. These agents are highly cytotoxic against B-cell lymphoid cells and are evaluated in CLL.
Lumiliximab (anti-CD23 mAb) is a genetically engineered macaque-human
immunoglobulin (Ig) A1. This antibody showed high activity and good tolerability in phase I clinical trial and is evaluated in phase I/II clinical trials as a single agent and in combination.
Epratuzumab is a humanized anti-CD22 mAb currently used in clinical trials for treatment of
non-Hodgkin lymphoma and autoimmune disorders. Further studies are needed to elucidate the role of this agent in CLL.
Apolizumab (
HU1D10) is a humanized
IgG1 antibody specific for a polymorphic determinant found on the HLA-DRbeta chain. Preclinical and early clinical studies suggest that this mAb has some activity in CLL.
HCD122 (CHIR-12.12) and
SGN-40 are anti-CD40 mAbs which induce cytotoxicity against CLL cells. Phase I study has shown a favorable safety profile and some activity of
HCD122 in pretreated CLL patients.
Immunotoxins, especially BL22, LMP-2 and
denileukin diftitox, are also being evaluated in lymphoid
malignancies and seem to be active in CLL. Finally, antiangiogenic mAbs, especially bevacimzumab, have a potential therapeutic role in this disease. In this review, new mAbs, potentially useful in CLL are presented.