Antibody-targeted therapy for low-grade lymphoma

Monoclonal antibodies (MoAbs) have now become a successful treatment for selected patients with non-Hodgkin's lymphoma (NHL). Antibody targets most commonly used for the treatment of B-cell NHL include CD20, CD19, and CD22. Unconjugated MoAbs are cytotoxic by several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and signal transduction leading to apoptosis. In an attempt to augment the effectiveness of naked antibody preparations, various radioconjugates, immunotoxins, chemotherapeutic agents, or immune-modifiers have been attached to the antibodies. The immunotoxin tested most extensively in clinical trials is B4-blocked ricin (anti-CD19 with a partially blocked ricin toxin). The use of radioimmunoconjugates to augment the effectiveness of unlabeled antibodies has been one of the most popular strategies. Antibodies against these targets have now been chelated with radioconjugates such as 131I or 90Y and tested in recent clinical trials. Radioimmunotherapy has the theoretical advantage over naked antibody therapy or immunotoxin therapy in that the MoAb conjugated with a radioisotope can have a "cross-fire" effect such that antigen-negative tumor cells adjacent to those expressing the target antigen may also be killed. This may enhance the likelihood of tumor sterilization even in fairly bulky disease. Future studies will focus on testing these antibodies in larger patient populations, sequentially or in combination, and on combining MoAb therapy with standard- or high-dose chemotherapy and hematopoietic stem-cell transplantation.