Selective killing of leukemia and lymphoma cells ectopically expressing hCGβ by a conjugate of curcumin with an antibody against hCGβ subunit

Abstract

Objective: A variety of cancers ectopically express human chorionic gonadotropin beta (hCGβ). Patients harboring such cancers have poor prognosis and adverse survival. A recombinant chimeric antibody, cPiPP, exhibiting high affinity and specificity for hCGβ/hCG was engineered. This study was designed to determine whether this antibody alone or conjugated to curcumin can selectively kill tumor cells expressing hCGβ. Experimental Design: The study was carried out on MOLT-4 and U-937 cells expressing hCGβ and on peripheral blood leukocytes of acute myeloid leukemia (AML) patients. The anticancerous compound curcumin was conjugated to cPiPP. The binding of cPiPP and cPiPP-curcumin conjugate to cells was studied by flow cytometry and cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), FACS with propidium iodide staining, trypan blue exclusion assay and microscopy. Results: The antibody did not impair the growth of MOLT-4 and U-937 cells in culture. Its conjugate with curcumin, however, was lethal to both cell lines. The immunoconjugate killed tumor cells bearing the CD33 marker of an AML patient expressing hCGβ but did not have a similar action on cells of another AML patient with the CD13 marker but who was negative for hCGβ. Conclusion: A humanized antibody against hCGβ linked to curcumin has potential for therapy of hCGβ-expressing tumors.