EXPRESSION OF INTERLEUKIN-6 RECEPTORS BY PEDIATRIC ACUTE LYMPHOBLASTIC-LEUKEMIA CELLS WITH THE T(4-11) TRANSLOCATION - A POSSIBLE TARGET FOR THERAPY WITH RECOMBINANT IL6-PSEUDOMONAS EXOTOXIN

We have detected expression of interleukin-6 receptors (IL-6R) by prim ary leukemic cells from three of six patients with t(4;11)+ ALL. Scatc hard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on th ese cells (median, 1560; mean, 1540). All three IL-6R+ cases also expr essed CD33, which was not expressed on IL-6R-negative cases. To determ ine if these receptors could serve as a target for a recombinant ligan d-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6 - Pseudomonas exotoxin (IL6-PE4E) fusion protein, in w hich the toxicity and specificity of the chimeric toxin was enhanced b y substitution of four glutamine residues for naturally occurring amin o acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE4E in a 48-h cytotoxicity assay, with ID50 values (concentra tions causing 50% decrease in viability) ranging from 23 ng/ml to 92 n g/ml (median, 61; mean, 58). Furthermore, incubation of these cells wi th 10(3) ng/ml IL6-toxin for 24 h prevented their subsequent engraftme nt in SCID mice. Thus, IL6-PE4E may be useful for ex vivo purging of I L-6R+ leukemic cells in an autologous bone marrow transplantation sett ing and possibly for therapy of residual, chemotherapy-resistant disea se.