Selective killing of leukemia and lymphoma cells ectopically expressing hCGbeta by a conjugate of curcumin with an antibody against hCGbeta subunit.
OBJECTIVE
A variety of cancers ectopically express human chorionic gonadotropin beta (hCGbeta). Patients harboring such cancers have poor prognosis and adverse survival. A recombinant chimeric antibody, cPiPP, exhibiting high affinity and specificity for hCGbeta/hCG was engineered. This study was designed to determine whether this antibody alone or conjugated to curcumin can selectively kill tumor cells expressing hCGbeta.


METHODS
The study was carried out on MOLT-4 and U-937 cells expressing hCGbeta 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 hCGbeta but did not have a similar action on cells of another AML patient with the CD13 marker but who was negative for hCGbeta.


CONCLUSIONS
A humanized antibody against hCGbeta linked to curcumin has potential for therapy of hCGbeta-expressing tumors.
Vyas
Hemant K
HK
Talwar Research Foundation, New Delhi, India.
Pal
Rahul
R
Vishwakarma
Ram
R
Lohiya
Nirmal K
NK
Talwar
G P
GP
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002469:Cell Separation; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000378:metabolism*; D003474:Curcumin / Q000378:metabolism*; D015195:Drug Design; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D063268:Sialic Acid Binding Ig-like Lectin 3; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D020298:U937 Cells
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D018997:Chorionic Gonadotropin, beta Subunit, Human; D063268:Sialic Acid Binding Ig-like Lectin 3; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D003474:Curcumin