Laboratory and clinical applications of monoclonal antibodies for leukemias and non-Hodgkin's lymphomas.
Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T-cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. After using all of the aforementioned markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-CD20 and anti-CD19 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B-cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-CD7, anti-CD5, and antibodies that separate T lymphocytes subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphological classification. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs have shown promise. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.
Foon
K A
KA
Division of Clinical Immunology, Roswell Park Memorial Institute, Buffalo, New York.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000954:Antigens, Surface / Q000032:analysis; D006801:Humans; D007938:Leukemia / Q000175:diagnosis* / Q000628:therapy; D007945:Leukemia, Lymphoid / Q000145:classification; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000628:therapy
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface