Ss. Joshi et al., Antitumor therapeutic potential of activated human umbilical cord blood cells against leukemia and breast cancer, CLIN CANC R, 6(11), 2000, pp. 4351-4358
In this study, in vitro and lit vivo antitumor effects of mononuclear cells
from human umbilical cord blood cells (UCBCs) acid peripheral blood stem c
ells (PBCs) harvest obtained by leukapheresis were compared. Interleukin 2
(IL-2)-activated mononuclear tells from UCBCs showed increased cytotoxicity
against K562 and Raji hematopoietic malignant cells compared with PBCs (P
< 0.05), After IL-2 activation, both UCBCs and PBCs showed significant cyto
toxicity against MDA-231 human breast cancer cells. The UCBC population inv
olved in this antitumor activity appeared to be CD56(+) natural killer prec
ursors. The cytotoxicity of UCBCs was inhibited in the absence of Ca2+(P <
0.05), supporting a pcr perforin/granzyme-mediated target of cell lysis, In
addition, antibodies to Fas ligand blocked cytotoxic activity, suggesting
that some of the antitumor cytotoxicity was Fas ligand mediated. In vivo an
titumor effects of UCBCs and PRCs were studied using a human leukemic cell-
bearing severe combined immunodeficient mouse model. There was a significan
t increase in the survival of K562 leukemia-bearing mice that also received
5 million ill vitro IL-2-activated UCBCs or PBCs i.v. on days 3 and day 5
after tumor transplantation compared with untreated mice (P < 0.01), Simila
r antitumor cytotoxicity of UCBCs and PBCs was also observed against MDA-23
1 human breast cancer grown in severe combined immunodeficient mice (P < 0.
01), These studies suggest that IL-2-activated UCBCs may be a useful source
of cellular therapy for patients with hematological malignancies and breas
t cancer.