Reactivity of Human Monoclonal Antibody Campath-1 with Human Leukemia Lymphoma Cell Lines of Varying Maturation

Abstract

Human leukemia-lymphoma cell lines reflecting hematopoietic clones at various stages of differentiation were examined for binding and complement mediated lysis by Campath-1. Expression of the cell surface antigen was determined with fluorescein isothiocyanate conjugated Campath-1, by ultraviolet microscopy and with a fluorescent activated cell sorter (FACS). The results indicate that there is a correlation between Campath-1 binding and the stage of lymphoid-cell differentiation. The null and T lines bound Campath-1 weakly and the fluorescence intensity was low. In the B lines there was a gradual increase in labelling correlating with the stage of differentiation. The redistribution pattern of Campath-1 on the membrane of null and T lines was in the form of rings and small caps whereas that on the B lines was that of moderate patches. Complement mediated cytolysis occurred with the majority of the cell lines, but did not correlate with the extent of surface antibody binding nor with the stage of lymphoid differentiation. The recovery and proliferative capacity of the residual cells after treatment with Campath-1 and complement was low for the null and T lines. This was variable for the B lines, but some did not regain proliferative capacity, whereas others recovered after treatment. The present results suggest that Campath-1 may have considerable utility in marrow depletion of residual. leukemic cells, more specifically of null and T-cell origin, prior to autologous transplantation. Determination of both the sensitivity of the patient's leukemic: cells to cytolysis and the recovery of proliferative capacity of Campath-1 resistant cells may contribute essential information concerning the possible efficacy of purging with this antibody in patients with significant marrow involvement prior to transplantation.

Key Words:

• Campath-1
• leukemia lymphoma lines
• differentiation